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Find video protocols related to scientific articles indexed in Pubmed.
Identifying Genetic Variants for Addiction via Propensity Score Adjusted Generalized Kendall's Tau.
J Am Stat Assoc
PUBLISHED: 11-11-2014
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Identifying replicable genetic variants for addiction has been extremely challenging. Besides the common difficulties with genome-wide association studies (GWAS), environmental factors are known to be critical to addiction, and comorbidity is widely observed. Despite the importance of environmental factors and comorbidity for addiction study, few GWAS analyses adequately considered them due to the limitations of the existing statistical methods. Although parametric methods have been developed to adjust for covariates in association analysis, difficulties arise when the traits are multivariate because there is no ready-to-use model for them. Recent nonparametric development includes U-statistics to measure the phenotype-genotype association weighted by a similarity score of covariates. However, it is not clear how to optimize the similarity score. Therefore, we propose a semiparametric method to measure the association adjusted by covariates. In our approach, the nonparametric U-statistic is adjusted by parametric estimates of propensity scores using the idea of inverse probability weighting. The new measurement is shown to be asymptotically unbiased under our null hypothesis while the previous non-weighted and weighted ones are not. Simulation results show that our test improves power as opposed to the non-weighted and two other weighted U-statistic methods, and it is particularly powerful for detecting gene-environment interactions. Finally, we apply our proposed test to the Study of Addiction: Genetics and Environment (SAGE) to identify genetic variants for addiction. Novel genetic variants are found from our analysis, which warrant further investigation in the future.
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Smokers' sensory beliefs mediate the relation between smoking a 'light/low tar' cigarette and perceptions of harm.
Tob Control
PUBLISHED: 11-06-2014
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The sensory belief that 'light/low tar' cigarettes are smoother can also influence the belief that 'light/low tar' cigarettes are less harmful. However, the 'light' concept is one of several factors influencing beliefs. No studies have examined the impact of the sensory belief about one's own brand of cigarettes on perceptions of harm.
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Changes in tar yields and cigarette design in samples of Chinese cigarettes, 2009 and 2012.
Tob Control
PUBLISHED: 10-30-2014
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China is home to the greatest number of smokers as well as the greatest number of smoking-related deaths. An active and growing market of cigarettes marketed as 'light' or 'low tar' may keep health-concerned smokers from quitting, wrongly believing that such brands are less harmful.
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Potential Mechanisms of Benzyl Isothiocyanate Suppression of Invasion and Angiogenesis by the U87MG Human Glioma Cell Line.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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Glioma is one of the most common tumors in China and chemotherapy is critical for its treatment. Recent studies showed that benzyl isothiocyanate (BITC) could inhibit the growth of glioma cells, but the mechanisms are not fully understood. This study explored the inhibitory effect of BITC on invasion and angiogenesis of U87MG human glioma cells in vitro and in vivo, as well as potential mechanisms. It was found that BITC could inhibit invasion and angiogenesis of human glioma U87MG cells by inducing cell cycle arrest at phase G2/M. It also was demonstrated that BITC decreased expression of cyclin B1, p21, MMP-2/9, VE-cadherin, CD44, CXCR4 and MTH1, the activity of the telomerase and PKC? pathway. Microarray analysis was thus useful to explore the potential target genes related to tumorigenic processes. BITC may play important roles in the inhibition of invasion and angiogenesis of human glioma cells.
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Toxic metal and nicotine content of cigarettes sold in China, 2009 and 2012.
Tob Control
PUBLISHED: 10-23-2014
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Metals of primary health concern can accumulate in the tobacco plant and contribute to smokers' exposures to carcinogens, a significant cause of the millions of smoking-related deaths in China each year. These exposures are due to the smoker's addiction to nicotine.
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[Research progress of the natural small molecular products synergistically with antifungal agents to inhibit drug-resistant fungi].
Yao Xue Xue Bao
PUBLISHED: 10-18-2014
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The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary (intrinsic) or secondary (acquired) resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fungi.
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Evaluation of characteristics and surgical outcomes in cervical spondylotic amyotrophy.
Indian J Orthop
PUBLISHED: 10-10-2014
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Cervical spondylotic amyotrophy (CSA) is a rare clinical syndrome resulting from cervical spondylosis. Surgical treatment includes anterior cervical decompression and fusion (ACDF), and laminoplasty with or without foraminotomy. Some studies indicate that ACDF is an effective method for treating CSA because anterior decompression with or without medial foraminotomy can completely eliminate anterior and/or anterolateral lesions. We retrospectively evaluated outcome of surgical outcome by anterior cervical decompression and fusion (ACDF).
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[Effect of ABA on transcriptionally active Ty1-copia retrotransposons in Dendrobium officinale].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-07-2014
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Using universal primer Tyl-copia retrotransposon RT, the conserved reverse transcriptase domain of about 260 bp was amplified by RT-PCR from the Dendrobium officinale which induced by 100 micromol x L(-1) abscisic acid (ABA), indicating these retrotransposons activated by 100 micromol x L(-1) ABA. The amplicons were recovered and cloned,then sequenced and analyzed by related bioinformatics software. Forty-two Ty1-copia like retrotransposon RT transcriptionally activated were obtained with high heterogeneity. The length of these sequences varied from 247 to 266 bp, and was rich in AT and homology ranged from 46.3% to 98.9%. The same to Ty1-copia like retrotransposon RT of genome, different c/s-acting regulatory elements induced by stress conditions and the starting transcription signals, corresponding to CAAT box, TATA box conserved sequences and some other regulatory elements. The c/s-acting regulatory elements induced by stress conditions of reverse transcriptase transcriptionally activated of Tyl-copia retrotransposons were significantly increased than that of Ty1-copia like retrotransposon RT of genome. When being translated into amino acids, fifteen sequences presented stop codon mutation, nineteen sequences presented frameshift mutation, and all sequences presented conserved sequence "SLYGKQ" mutation. Five categories were identified through phylogenic analysis after alignment analyses of their amino acid sequences, and with Ty1-copia like retrotransposon RT of genome having low homology, which indicated that reverse transcriptase transcriptionally activated of Ty1-copia retrotransposons which induced by ABA had Significantly differences with Ty1-copia like retrotransposon RT of genome.
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Folate-decorated and reduction-sensitive micelles assembled from amphiphilic polymer-camptothecin conjugates for intracellular drug delivery.
Mol. Pharm.
PUBLISHED: 10-03-2014
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It is one of the challenges for a wide clinical application of polymer micelles to address the structure disintegration and premature drug release before reaching a pathological site. In the current study, folic acid (FA)-decorated polymer-drug conjugates (FSC) were synthesized with disulfide linkages between camptothecin (CPT) and amphiphilic poly(ethylene glycol)-b-poly(?-caprolactone) (PECL) copolymers. FSC conjugates were proposed to assemble into micelles with a hydrophobic core of PCL segments and CPT and a hydrophilic corona of PEG segments. The addition of hexadecanol during micelle formation (FSC-16) was proposed to modulate the interactions of hydrophobic segments in micelles and enhance the reductive sensitivity. FSC-16 micelles were obtained with critical micelle concentration of around 2 ?g/mL and an average size of around 200 nm, and the conjugated CPT was rapidly released out in response to glutathione. The reductive sensitivity was also demonstrated with respect to the changes of micelle size and morphologies as well as the fluorescent intensity of pyrene loaded in micelles. Benefiting from the FA receptor-mediated uptake and the reduction-sensitive release of CPT, significant cytotoxicity and cell apoptosis were identified for FSC-16 micelles against SKOV-3 cells with strong expressions of FA receptors. Flow cytometry and confocal laser scanning microscopy analyses demonstrated that CPT was distributed into nuclei after cellular uptake and intracellular release from FSC-16 micelles. Thus, the FA-decorated and reduction-sensitive micelles assembled from polymer-drug conjugates show advantages in inhibiting premature release during circulation, enhancing cellular uptake at the tumor tissues, and promoting intracellular release and nuclei location of the active moieties.
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Screening and Identification of DNA Aptamers against T-2 Toxin Assisted by Graphene Oxide.
J. Agric. Food Chem.
PUBLISHED: 09-30-2014
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A high-affinity ssDNA aptamer that specifically binds to T-2 toxin was generated by the systemic evolution of ligands by exponential enrichment (SELEX) procedure assisted by graphene oxide (GO). After 10 rounds of selection against T-2 toxin, a highly enriched ssDNA pool was sequenced and the representative aptamers were subjected to binding assays to evaluate their affinity and specificity. Circular dichroism spectroscopy was also used to study the inherent interaction of T-2 toxin and the preferred aptamer Seq.16, which demonstrated a low dissociation constant (Kd) of 20.8 ± 3.1 nM and excellent selectivity for T-2 toxin. Using the selected aptamer Seq.16 as the recognition element, an aptamer-based fluorescent bioassay was developed for the measurement of T-2 in beer samples with a linear range from 0.5 to 37.5 ?M (R(2) = 0.988) and a limit of detection (LOD) of 0.4 ?M. The results indicate that GO-SELEX technology is appropriate for the screening of aptamers against small-molecule toxins, offering a promising application for aptamer-based biosensors.
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RASAL2 down-regulation in ovarian cancer promotes epithelial-mesenchymal transition and metastasis.
Oncotarget
PUBLISHED: 09-13-2014
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Ovarian cancer is the most lethal gynecologic malignancy, and transcoelomic metastasis is responsible for the greatest disease mortality. Although intensive efforts have been made, the mechanism behind this process remains unclear. RASAL2 is a GTPase activating proteins (GAPs) which was recently reported as a tumor suppressor in breast cancer. In this study, we identified RASAL2 as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in ovarian cancer. RASAL2 was down-regulated in ovarian cancer samples compared with normal tissue samples, especially in advanced stages and grades. RASAL2 knockdown in ovarian cancer cell lines promoted in vitro anchorage-independent growth, cell migration and invasion and in vivo tumor formation. Moreover, we observed EMT in RASAL2-depleted cells. E-cadherin-mediated cell-cell adhesion was attenuated, and mesenchymal markers were up-regulated. Further investigation revealed that the oncogenic role of RASAL2 down-regulation was mediated by the Ras-ERK pathway. RASAL2 knockdown activated the Ras-ERK pathway, and inhibition of the pathway reversed the functional effects of RASAL2 depletion. Together, our results implicate RASAL2 as an EMT regulator and tumor suppressor in ovarian cancer, and down-regulation of RASAL2 promotes ovarian cancer progression.
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Venous thromboembolism risk factors in Chinese non-small cell lung cancer patients.
Support Care Cancer
PUBLISHED: 08-27-2014
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Certain clinicopathological factors contribute to the development of venous thromboembolism (VTE) in lung cancer. The aim of the current study was to assess the incidence of and the potential risk factors associated with the development of VTE in Chinese lung cancer patients.
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Efficacy and safety of intravesical onabotulinumtoxinA injection on elderly patients with chronic central nervous system lesions and overactive bladder.
PLoS ONE
PUBLISHED: 08-22-2014
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Intravesical injection of onabotulinumtoxinA is an effective treatment for overactive bladder (OAB). Nonetheless, the treatment outcome is unclear in OAB patients with central nervous system (CNS) lesions. This study evaluated the efficacy and safety of intravesical onabotulinumtoxinA treatment in elderly patients with chronic cerebrovascular accidents (CVAs), Parkinson's disease (PD) and dementia.
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Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC "click" chemistry as potential anticancer agents.
Drug Des Devel Ther
PUBLISHED: 08-06-2014
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A series of novel derivatives of phenyl-substituted berberine triazolyls has been designed and synthesized via copper-catalyzed azide-alkyne cycloaddition click chemistry in an attempt to develop antitumor agents. All of the compounds were evaluated for anticancer activity against a panel of three human cancer cell lines, including MCF-7 (breast), SW-1990 (pancreatic), and SMMC-7721 (liver) and the noncancerous human umbilical vein endothelial cell (HUVEC) cell lines. The results indicated that most of the compounds displayed notable anticancer activities against the MCF-7 cells compared with berberine. Among these derivatives, compound 16 showed the most potent inhibitory activity against the SW-1990 and SMMC-7721 cell lines, with half-maximal inhibitory concentration (IC50) values of 8.54±1.97 ?M and 11.87±1.83 ?M, respectively. Compound 36 exhibited the most potent inhibitory activity against the MCF-7 cell line, with an IC50 value of 12.57±1.96 ?M. Compound 16 and compound 36 exhibited low cytotoxicity in the HUVEC cell line, with IC50 values of 25.49±3.24 ?M and 30.47±3.47 ?M. Furthermore, compounds 14, 15, 16, 17, 18, 32, and 36 exhibited much better selectivity than berberine toward the normal cell line HUVEC.
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Hemocompatibility and anti-biofouling property improvement of poly(ethylene terephthalate) via self-polymerization of dopamine and covalent graft of lysine.
J Biomater Sci Polym Ed
PUBLISHED: 07-30-2014
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Inspired by the composition of adhesive proteins in mussels, we used self-polymerized dopamine to form a thin and surface-adherent polydopamine layer onto poly(ethylene terephthalate) (PET) sheet, followed by covalently grafting lysine (Lys) to improve hemocompatibility and anti-biofouling property. The obtained surfaces were characterized by water contact angle measurements, attenuated total reflectance Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy analysis. The results of platelet adhesion and protein adsorption tests showed that Lys-immobilized PET was endowed with improved resistance to nonspecific protein adsorption and platelet adhesion. Cell assay results showed that PET-g-Lys surface could greatly inhibit NIH 3T3 cell adhesion. These works provide a facile hemocompatible and anti-fouling surface for biomedical applications.
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Targeted metabolomic study indicating glycyrrhizin’s protection against acetaminophen-induced liver damage through reversing fatty acid metabolism.
Phytother Res
PUBLISHED: 07-18-2014
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The present study aimed to give a short report on a possible mechanism of glycyrrhizin to acetaminophen-induced liver toxicity. Seven-day intraperitoneal administration of glycyrrhizin (400 mg/kg/day) to 2- to 3-month-old male C57BL/6N mice (mean weight 27 g) significantly prevents acetaminophen-induced liver damage, as indicated by the activity of alanine transaminase and aspartate aminotransferase. Metabolomics analysis and principal component analysis (PCA) using ultra-fast liquid chromatography coupled to triple time-of-flight mass spectrometer were performed. PCA separated well the control, glycyrrhizin-treated, acetaminophen-treated, and glycyrrhizin+acetaminophen-treated groups. Long-chain acylcarnitines were listed as the top ions that contribute to this good separation, which include oleoylcarnitine, palmitoylcarnitine, palmitoleoylcarnitine, and myristoylcarnitine. The treatment of glycyrrhizin significantly reversed the increased levels of long-chain acylcarnitines induced by acetaminophen administration. In conclusion, this metabolomic study indicates a significant glycyrrhizin protection effect against acetaminophen-induced liver damage through reversing fatty acid metabolism.
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Electrophysiological differences between Hirayama disease, amyotrophic lateral sclerosis and cervical spondylotic amyotrophy.
BMC Musculoskelet Disord
PUBLISHED: 07-07-2014
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Hirayama disease (HD), amyotrophic lateral sclerosis (ALS) or cervical spondylotic amyotrophy (CSA) may result in atrophy of intrinsic hand and forearm muscles. The incidence of HD is low, and it is rarely encountered in the clinical setting. Consequently, HD is often misdiagnosed as ALS or CSA. It is important to differentiate these diseases because HD is caused by a benign focal lesion that is limited to the upper limbs.
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[Effect of controlled release fertilizer on nitrous oxide emission from paddy field under plastic film mulching cultivation].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 07-03-2014
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A field experiment was conducted to assess the effect of controlled release fertilizer on N2O emission in paddy field under plastic film mulching cultivation (PM) with water-saving irrigation. Results showed that in the rice growing season, cumulative N2O emissions from the plots applied with urea (PM+U) and with controlled release fertilizer (PM+CRF) were (38.2 +/- 4.4) and (21.5 +/- 5.2) mg N x m(-2), respectively. The N2O emission factors were 0.25% and 0.14% in the treatments PM+U and PM+CRF, respectively. The controlled release fertilizer decreased the total N2O emission by 43.6% compared with urea, of which 49.6% was reduced before the drying period. It also reduced the peak of N2O emission by 52.6%. However, it did not affect soil microbial biomass N and soil NH(4+)-N content at any rice growing stage, and grain yield either. No significant correlation was observed between N2O flux and soil Eh or soil temperature at the depth of 5 cm.
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Increased methylation at differentially methylated region of GNAS in infants born to gestational diabetes.
BMC Med. Genet.
PUBLISHED: 06-26-2014
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BackgroundOffspring of pregnancy complicated with gestational diabetes (GDM) are at high risk for metabolic diseases. The mechanisms behind the association of intrauterine exposure to GDM and high risk of health problems in later life remain largely unknown. The aim of this study was to clarify the alteration in methylation levels at differentially methylated regions (DMRs) of GNAS and IGF2 in fetuses of GDM women and to explore the possible mechanisms linking maternal GDM with high risk of metabolic diseases in later life of GDM offspring.MethodsThe methylation levels were detected in 7 CpG sites of GNAS DMRs and 6 sites of IGF2 DMRs. Methylation levels were significantly higher at sites 4, 5 and 7 of GNAS DMR in GDM compared to normal pregnancy (P¿=¿0.007, 0.008 and 0.008, respectively). The methylation level at site 4 of GNAS was significantly correlated with the presence of GDM (P¿=¿0.003), the methylation levels at site 5 and 7 were significantly correlated with the presence of GDM (P¿=¿0.002 for both) and gestational age (P¿=¿0.027 for both). There were no significant difference in any sites of IGF2 DMR (P¿>¿0.05 for all).ResultsLymphocytes were isolated from umbilical cord blood of infants born to 87 women with GDM and 81 women with normal pregnancy. Genomic DNA was extracted and DNA methylation levels of GNAS and IGF2 DMRs were determined by Massarray quantitative methylation analysis.ConclusionsWe concluded maternal GDM-induced hypermethylation at GNAS DMR and this condition may be among the mechanisms associating maternal GDM with increased risk of metabolic diseases in later life of offspring.
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T8590C polymorphism of CYP4A11 is a risk factor for hypertension: a meta-analysis.
Chin. Med. J.
PUBLISHED: 06-17-2014
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T8590C polymorphism of CYP4A11 has been associated with hypertension, though with conflicting results. The aim of this study was to quantitatively summarize the evidence for CYP4A11 T8590C polymorphism and hypertension risk.
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Determinants of smoking-induced deprivation in China.
Tob Control
PUBLISHED: 05-16-2014
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Spending on cigarettes may deprive households of other items like food. The goal of this study was to examine the prevalence of and factors associated with this smoking-induced deprivation among adult smokers in China.
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Elevated Serum IgE May be Associated with Development of Ketamine Cystitis.
J. Urol.
PUBLISHED: 05-13-2014
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Previous studies revealed bladder mast cell and eosinophil cell infiltration in patients with ketamine cystitis. Due to possible hypersensitivity in those with this condition we investigated the association of serum Ig, histology findings and symptoms in patients with ketamine cystitis.
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Impact of the 'Giving Cigarettes is Giving Harm' campaign on knowledge and attitudes of Chinese smokers.
Tob Control
PUBLISHED: 05-13-2014
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To date there is limited published evidence on the efficacy of tobacco control mass media campaigns in China. This study aimed to evaluate the impact of a mass media campaign 'Giving Cigarettes is Giving Harm' (GCGH) on Chinese smokers' knowledge of smoking-related harms and attitudes towards cigarette gifts.
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Potential therapeutic effect of intravesical botulinum toxin type?A on bladder pain syndrome/interstitial cystitis.
Int. J. Urol.
PUBLISHED: 05-09-2014
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Bladder pain syndrome/interstitial cystitis is characterized by bladder pain associated with urgency, frequency, nocturia, dysuria and sterile urine. Recent studies have shown that these bladder dysfunctions could originate from chronic inflammation or urothelial insult and proceed to a cascade of tissue reactions, which finally ascends to the central nervous system. Pilot studies of intravesical injection of botulinum toxin type?A for bladder pain syndrome/interstitial cystitis had been introduced since 2005 with a promising result. Recent evidence suggests that botulinum toxin type?A could significantly improve symptoms such as daytime frequency, nocturia, pain, quality of life and bladder capacity in bladder pain syndrome/interstitial cystitis patients. Single injection of botulinum toxin could not achieve long-term successful therapeutic result, and repeat injections could provide a better long-term success rate. However, patients with ulcer type bladder pain syndrome/interstitial cystitis might not gain a benefit from botulinum toxin type?A injection. Laboratory evidence showed that botulinum toxin type?A for bladder pain syndrome/interstitial cystitis injection could induce peripheral desensitization, reduces bladder chronic inflammation and decreases apoptotic signal molecules in the urothelium. The present article reviewed the recent advances of botulinum toxin type?A on bladder pain syndrome/interstitial cystitis.
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Molecular genetic techniques for gene manipulation in Candida albicans.
Virulence
PUBLISHED: 04-23-2014
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Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains.
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Effect of photodynamic therapy with hypocrellin B on apoptosis, adhesion, and migration of cancer cells.
Int. J. Radiat. Biol.
PUBLISHED: 04-23-2014
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In the present study, we investigated effects of photodynamic therapy with hypocrellin B on apoptosis, adhesion, and migration of cancer cells in vitro.
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Magnetic resonance neurography in analysis of operative safety of transforaminal lumbar interbody fusion in Chinese subjects.
Orthop Surg
PUBLISHED: 04-08-2014
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To measure relevant anatomical variables of lumbosacral nerve root and adjacent structures by magnetic resonance neurography (MRN) and analyze operative safety of transforaminal lumbar interbody fusion (TLIF) in Chinese subjects.
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Urothelial dysfunction and chronic inflammation in patients with spinal cord injuries at different levels and correlation with urodynamic findings.
Neurourol. Urodyn.
PUBLISHED: 03-30-2014
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To investigate urothelial dysfunction and suburothelial inflammation in patients with chronic SCI at different spinal cord levels.
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[Targeting microRNA-mediated suppression of vascular endothelial growth factor gene expression and proliferation in malignant melanoma cells in vitro].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 03-28-2014
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To explore the inhibitory effect of targeting miRNA on the expression of vascular endothelial growth factor (VEGF) and cell proliferation in malignant melanoma (MM) SKmel-28 cells.
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Conformational dynamics of human FXR-LBD ligand interactions studied by hydrogen/deuterium exchange mass spectrometry: insights into the antagonism of the hypolipidemic agent Z-guggulsterone.
Biochim. Biophys. Acta
PUBLISHED: 02-25-2014
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Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of transcription factors that plays a key role in the regulation of bile acids, lipid and glucose metabolisms. The regulative function of FXR is governed by conformational changes of the ligand binding domain (LBD) upon ligand binding. Although FXR is a highly researched potential therapeutic target, only a limited number of FXR-agonist complexes have been successfully crystallized and subsequently yielded high resolution structures. There is currently no structural information of any FXR-antagonist complexes publically available. We therefore explored the use of amide hydrogen/deuterium exchange (HDX) coupled with mass spectrometry for characterizing conformational changes in the FXR-LBD upon ligand binding. Ligand-specific deuterium incorporation profiles were obtained for three FXR ligand chemotypes: GW4064, a synthetic non-steroidal high affinity agonist; the bile acid chenodeoxycholic acid (CDCA), the endogenous low affinity agonist of FXR; and Z-guggulsterone (GG), an in vitro antagonist of the steroid chemotype. A comparison of the HDX profiles of their ligand-bound FXR-LBD complexes revealed a unique mode of interaction for GG. The conformational features of the FXR-LBD-antagonist interaction are discussed.
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Smoking-related thoughts and microbehaviours, and their predictive power for quitting.
Tob Control
PUBLISHED: 02-25-2014
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Negative attitudes to smoking are well-established predictors of intentions to quit and quit behaviours, but less attention has been given to whether quitting is influenced by smoking-related thoughts and microbehaviours that reflect a concern about smoking.
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Value of multidetector computed tomography in the diagnosis of mucosa-associated lymphoid tissue-lymphomas in the parotid gland: A case report and review of the literature.
Oncol Lett
PUBLISHED: 02-13-2014
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The present study aimed to review the multidetector computed tomography (MDCT) imaging features of eight mucosa-associated lymphoid tissue (MALT)-lymphoma cases of the parotid gland and to explore the diagnostic value of MDCT. A total of eight patients with pathologically confirmed MALT-lymphomas of the parotid gland underwent pre-operative MDCT plain and dual-phase scans. The changes in the CT values and enhancement patterns of the tumors were assessed. Quantitative analysis was performed to determine the CT value changes of the tumors in the various enhanced phases compared with the plain scan. The MALT-lymphomas of the parotid gland exhibited even density isodense or hyperdense nodules, with occasional calcification and necrosis. The dual-phase scan of the MALT-lymphomas revealed a pattern of lower or moderate enhancement, circumambient enhancement or delayed enhancement. The MALT-lymphomas were closely associated with Sjögre's syndrome and demonstrated malignant features and isodense or hyperdense nodules and lower or moderate enhancement on the CT scans.
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In vitro and in vivo activities of pterostilbene against Candida albicans biofilms.
Antimicrob. Agents Chemother.
PUBLISHED: 02-10-2014
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Pterostilbene (PTE) is a stilbene-derived phytoalexin that originates from several natural plant sources. In this study, we evaluated the activity of PTE against Candida albicans biofilms and explored the underlying mechanisms. In 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assays, biofilm biomass measurement, confocal laser scanning microscopy, and scanning electron microscopy, we found that ?16 ?g/ml PTE had a significant effect against C. albicans biofilms in vitro, while it had no fungicidal effect on planktonic C. albicans cells, which suggested a unique antibiofilm effect of PTE. Then we found that PTE could inhibit biofilm formation and destroy the maintenance of mature biofilms. At 4 ?g/ml, PTE decreased cellular surface hydrophobicity (CSH) and suppressed hyphal formation. Gene expression microarrays and real-time reverse transcription-PCR showed that exposure of C. albicans to 16 ?g/ml PTE altered the expression of genes that function in morphological transition, ergosterol biosynthesis, oxidoreductase activity, and cell surface and protein unfolding processes (heat shock proteins). Filamentation-related genes, especially those regulated by the Ras/cyclic AMP (cAMP) pathway, including ECE1, ALS3, HWP1, HGC1, and RAS1 itself, were downregulated upon PTE treatment, indicating that the antibiofilm effect of PTE was related to the Ras/cAMP pathway. Then, we found that the addition of exogenous cAMP reverted the PTE-induced filamentous growth defect. Finally, with a rat central venous catheter infection model, we confirmed the in vivo activity of PTE against C. albicans biofilms. Collectively, PTE had strong activities against C. albicans biofilms both in vitro and in vivo, and these activities were associated with the Ras/cAMP pathway.
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Berberine inhibits fluphenazine-induced up-regulation of CDR1 in Candida albicans.
Biol. Pharm. Bull.
PUBLISHED: 02-05-2014
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Over-expression of the Candida drug resistance gene CDR1 is a common mechanism generating azole-resistant Candida albicans in clinical isolates. CDR1 is transcriptionally activated through the binding of the transcription factor Tac1p to the cis-acting drug-responsive element (DRE) in its promoter. We previously demonstrated that the combination of fluconazole (FLC) and berberine (BBR) produced significant synergy when used against FLC-resistant C. albicans in vitro. In this study, we found that BBR inhibited both the up-regulation of CDR1 mRNA and the transport function of Cdr1p induced by fluphenazine (FNZ). Further, electrophoretic mobility shift assays suggested that the transcription activation complex of protein-DRE was disrupted by BBR, and electrospray ionization mass spectrometry analysis showed that BBR bound to the DRE of CDR1. Thus we propose that BBR inhibits the FNZ-induced transcriptional activation of CDR1 in C. albicans by blocking transcription factor binding to the DRE of CDR1. These results contribute to our understanding of the mechanism of synergistic effect of BBR and FLC.
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Ste18p is a positive control element in the mating process of Candida albicans.
Eukaryotic Cell
PUBLISHED: 01-31-2014
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Heterotrimeric G proteins are an important class of eukaryotic signaling molecules that have been identified as central elements in the pheromone response pathways of many fungi. In the fungal pathogen Candida albicans, the STE18 gene (ORF19.6551.1) encodes a potential ? subunit of a heterotrimeric G protein; this protein contains the C-terminal CAAX box characteristic of ? subunits and has sequence similarity to ? subunits implicated in the mating pathways of a variety of fungi. Disruption of this gene was shown to cause sterility of MTLa mating cells and to block pheromone-induced gene expression and shmoo formation; deletion of just the CAAX box residues is sufficient to inactivate Ste18 function in the mating process. Intriguingly, ectopic expression behind the strong ACT1 promoter of either the G? or the G? subunit of the heterotrimeric G protein is able to suppress the mating defect caused by deletion of the G? subunit and restore both pheromone-induced gene expression and morphology changes.
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Responses to crizotinib in a patient with c-ros oncogene 1, receptor tyrosine kinase-positive advanced lung adenocarcinoma: A case report.
Oncol Lett
PUBLISHED: 01-29-2014
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Rearrangements to the c-ros oncogene 1, receptor tyrosine kinase (ROS1) gene are reported in 1-2% of lung adenocarcinomas. These rearrangements are associated with a response to the small-molecule tyrosine kinase inhibitor crizotinib. ROS1 rearrangements can be detected using fluorescence in situ hybridization (FISH), which is considered the gold standard technique in detecting ROS1 rearrangements, and determining whether a patient would respond well to crizotinib treatment. However, FISH is an expensive and time-consuming assay, requiring specialized microscopy equipment and some level of technical expertise. The present report describes the case of a patient with advanced lung adenocarcinoma, who was identified to be negative for ROS-1 rearrangements by FISH, but positive by immunohistochemistry (IHC). The health of the patient improved following treatment with crizotinib. These results indicate that IHC assay could be an alternative option for the detection of ROS1 gene rearrangements.
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Hemocompatibility improvement of poly(ethylene terephthalate) via self-polymerization of dopamine and covalent graft of zwitterions.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 01-18-2014
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Poly (ethylene terephthalate) (PET) has been widely adopted as a scaffold biomaterial, but further hemocompatibility improvement is still needed for wide biomedical applications. Inspired by the composition of adhesive proteins in mussels, we propose to use self-polymerized dopamine to form a surface-adherent polydopamine layer onto PET sheet, followed by Michael addition with N,N-dimethylethylenediamine (DMDA) to build tertiary amine, and final zwitterions(sulfobetaine and carboxybetaine) construction through ring-opening reaction. Physicochemical properties of substrates were demonstrated by water contact angle measurement, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The hemocompatibility was evaluated by platelet adhesion, hemolytic, and protein adsorption. The results showed that the zwitterions immobilized PET endowed with improved resistance to nonspecific protein adsorption and platelet adhesion as well as nonhemolytic. The zwitterions with desirable hemocompatibility can be readily tailored to catheter for various biomedical applications.
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Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation.
Clin. Cancer Res.
PUBLISHED: 01-17-2014
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We investigated the incidence of concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in Chinese patients with non-small cell lung cancer (NSCLC), and assessed responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib in such tumors.
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Transposition of the Zorro2 retrotransposon is activated by miconazole in Candida albicans.
Biol. Pharm. Bull.
PUBLISHED: 01-07-2014
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Zorro2 is a member of a non-long terminal repeat (LTR) retrotransposon family in Candida albicans, but as yet no clear evidence has been provided to establish either transcription or transposition activity for Zorro2. In this study, the relative expression changes of two open reading frames in Zorro2, ORF19.7274 and ORF19.7275, were examined in response to miconazole (MCZ), and were found to be increased by this treatment. As well, the copy number and the transcripts of Zorro2 in MCZ-induced resistant daughter strains were increased compared to the parental strain, indicating that transposition of Zorro2 occurred during long-term MCZ treatment. Intriguingly, the transcription activity of Zorro2 retrotransposons was significantly inhibited when the cells were treated with MCZ together with antioxidant N-acetyl-L-cysteine (NAC). As both the level of intracellular reactive oxygen species (ROS) and the expression of genes involving DNA repair activated by MCZ were reduced when combined with the treatment of NAC, we propose that the damage caused by accumulation of ROS under MCZ stress is a major reason for the transcription and transposition activation of the Zorro2 retrotransposon.
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PINK1 and its familial Parkinson's disease-associated mutation regulate brain vascular endothelial inflammation.
J. Mol. Neurosci.
PUBLISHED: 01-03-2014
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Parkinson's disease (PD) is a debilitating disorder that affects movement. Inflammation-mediated endothelial dysfunction has been found to be involved in neurodegenerative diseases, including PD. More than 40 PTEN-induced putative kinase 1 (PINK1) mutations have been found in PD patients. The effects of PINK1 in vascular inflammation are as yet unknown. In this study, our findings revealed that PINK1 can be increased by the inflammatory cytokine tumor necrosis factor-? in primary human brain microvascular endothelial cells (HBMECs). We found that wild-type PINK1 prevents expression of the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), thus inhibiting the attachment of monocytes to brain endothelial cells. However, PINK1G309D, the loss-of-function mutation associated with early-onset familial PD, promotes expression of VCAM-1 and exacerbates attachment of monocytes to brain endothelial cells. Mechanism studies revealed that overexpression of wild-type PINK1 inhibits the VCAM-1 promoter by inhibiting the transcriptional activity of interferon regulatory factor 1 (IRF-1). However, PINK1G309D promotes the VCAM-1 promoter by increasing the transcriptional activity of IRF-1.
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Radial growth of two dominant montane conifer tree species in response to climate change in north-central china.
PLoS ONE
PUBLISHED: 01-01-2014
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North-Central China is a region in which the air temperature has clearly increased for several decades. Picea meyeri and Larix principis-rupprechtii are the most dominant co-occurring tree species within the cold coniferous forest belt ranging vertically from 1800 m to 2800 m a.s.l. in this region. Based on a tree-ring analysis of 292 increment cores sampled from 146 trees at different elevations, this study aimed to examine if the radial growth of the two species in response to climate is similar, whether the responses are consistent along altitudinal gradients and which species might be favored in the future driven by the changing climate. The results indicated the following: (1) The two species grew in different rhythms at low and high elevation respectively; (2) Both species displayed inconsistent relationships between radial growth and climate data along altitudinal gradients. The correlation between radial growth and the monthly mean temperature in the spring or summer changed from negative at low elevation into positive at high elevation, whereas those between the radial growth and the total monthly precipitation displayed a change from positive into negative along the elevation gradient. These indicate the different influences of the horizontal climate and vertical mountainous climate on the radial growth of the two species; (3) The species-dependent different response to climate in radial growth appeared mainly in autumn of the previous year. The radial growth of L. principis-rupprechtii displayed negative responses both to temperature and to precipitation in the previous September, October or November, which was not observed in the radial growth of P. meyeri. (4) The radial growth of both species will tend to be increased at high elevation and limited at low elevation, and L. principis-rupprechtii might be more favored in the future, if the temperature keeps rising.
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Increase in nontuberculous mycobacteria isolated in shanghai, china: results from a population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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In China, the prevalence of nontuberculous mycobacteria (NTM) in isolates from mycobacterial culture-positive patients with pulmonary tuberculosis (TB) is largely unknown.
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Urothelial dysfunction and increased suburothelial inflammation of urinary bladder are involved in patients with upper urinary tract urolithiasis - clinical and immunohistochemistry study.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate the urothelial dysfunction and inflammation of urinary bladder in patients with upper urinary tract (UUT) urolithiasis through the results of cystoscopic hydrodistension and immunohistochemistry study.
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First insight into the genotypic diversity of clinical Mycobacterium tuberculosis isolates from Gansu Province, China.
PLoS ONE
PUBLISHED: 01-01-2014
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Investigations of Mycobacterium tuberculosis genetic diversity in China have indicated a significant regional distribution. The aim of this study was to characterize the genotypes of clinical M. tuberculosis isolates obtained from Gansu, which has a special geographic location in China.
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Decrease of urinary nerve growth factor but not brain-derived neurotrophic factor in patients with interstitial cystitis/bladder pain syndrome treated with hyaluronic acid.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate urinary nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in interstitial cystitis/bladder pain syndrome (IC/BPS) patients after hyaluronic acid (HA) therapy.
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An assessment of health risks and mortality from exposure to secondhand smoke in Chinese restaurants and bars.
PLoS ONE
PUBLISHED: 01-01-2014
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Smoking is generally not regulated in restaurants or bars in China, or the restrictions are not fully implemented if there are any, while the related hazard health effects are not recognized by the majority of the Chinese population.
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Hydrazine-promoted sequential cation exchange: a novel synthesis method for doped ternary semiconductor nanocrystals with tunable emission.
Nanotechnology
PUBLISHED: 12-12-2013
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Using ZnSe nanocrystals (NCs) as starting material, Ag-doped or Cu-doped ZnCdSe ternary NCs were prepared by hydrazine-promoted sequential cation exchange in aqueous media. The composition of the NCs can be flexibly controlled by varying the amount of intermediate Ag or Cu cation addition, thus changing the emission of the ternary NCs while preserving the NC size. According to Vegards law, the as-prepared ternary NCs possess an alloyed structure. In addition, the ternary NCs obtained have a high quantum yield, strong stability and a broad optical tuning range.
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Rolling Up the Sheet: Constructing Metal-Organic Lamellae and Nanotubes from a [{Mn3(propanediolato)2}(dicyanamide)2]n Honeycomb Skeleton.
J. Am. Chem. Soc.
PUBLISHED: 12-02-2013
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Target synthesis of metal-organic nanotubes (MONTs) through a classic "rolling-up" mechanism remains a big challenge for coordination chemists. In this work, we report three 2D lamellar compounds and one (4,0) zigzag MONT based on a common honeycomb coordination skeleton. Our synthetic strategy toward sheet/tube superstructure transformation is to asymmetrically modify the inter-layer interactions by gradually increasing the size of the amine templates. Eventually, to relieve the surface tension of individual layers and to enhance surface areas and optimize host-guest interactions to accommodate bigger guests, spontaneous rolling up to form a tubular structure was achieved.
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Magnetoresistive polyaniline/multi-walled carbon nanotube nanocomposites with negative permittivity.
Nanoscale
PUBLISHED: 11-14-2013
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Contrary to the observed positive giant magnetoresistance (GMR) in as-received multi-walled carbon nanotubes (MWNTs), pure polyaniline (PANI) synthesized with Cr(vi) as oxidant and MWNTs/PANI nanocomposites with ammonium persulfate (APS) as oxidant, a room temperature negative GMR of around -2% was reported in MWNTs/PANI nanocomposites with Cr(vi) as oxidant. Different from a frequency switch of permittivity from negative to positive in MWNTs/PANI nanocomposites with APS as oxidant, unique negative permittivity was observed in MWNTs/PANI nanocomposites with Cr(vi) as oxidant within the measured frequency range from 20 to 2 × 10(6) Hz. The obtained unique negative permittivity was explained by the plasma frequency from the Drude model, at which the permittivity changes from negative to positive and the material changes from a metamaterial to an ordinary dielectric medium. The observed positive and negative GMR behaviors in these disordered systems as verified by the temperature dependent resistivity exploration were well explained through a wave-function shrinkage model and orbital magnetoconductivity theory by calculating the changed localization length (a0).
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Activation of the Wnt Pathway through AR79, a GSK3? Inhibitor, Promotes Prostate Cancer Growth in Soft Tissue and Bone.
Mol. Cancer Res.
PUBLISHED: 10-02-2013
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Due to its bone anabolic activity, methods to increase Wnt activity, such as inhibitors of dickkopf-1 and sclerostin, are being clinically explored. Glycogen synthase kinase (GSK3?) inhibits Wnt signaling by inducing ?-catenin degradation, and a GSK3? inhibitor, AR79, is being evaluated as an osteoanabolic agent. However, Wnt activation has the potential to promote tumor growth; therefore, the goal of this study was to determine if AR79 has an impact on the progression of prostate cancer. Prostate cancer tumors were established in subcutaneous and bone sites of mice followed by AR79 administration, and tumor growth, ?-catenin activation, proliferation, and apoptosis were assessed. Additionally, prostate cancer and osteoblast cell lines were treated with AR79, and ?-catenin status, proliferation (with ?-catenin knockdown in some cases), and proportion of ALDH(+)CD133(+) stem-like cells were determined. AR79 promoted prostate cancer tumor growth, decreased phospho-?-catenin, increased total and nuclear ?-catenin, and increased tumor-induced bone remodeling. Additionally, AR79 treatment decreased caspase-3 and increased Ki67 expression in tumors and increased bone formation in normal mouse tibiae. Similarly, AR79 inhibited ?-catenin phosphorylation, increased nuclear ?-catenin accumulation in prostate cancer and osteoblast cell lines, and increased proliferation of prostate cancer cells in vitro through ?-catenin. Furthermore, AR79 increased the ALDH(+)CD133(+) cancer stem cell-like proportion of the prostate cancer cell lines. In conclusion, AR79, while being bone anabolic, promotes prostate cancer cell growth through Wnt pathway activation. Implications: These data suggest that clinical application of pharmaceuticals that promote Wnt pathway activation should be used with caution as they may enhance tumor growth. Mol Cancer Res; 11(12); 1597-610. ©2013 AACR.
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Who purchases cigarettes from cheaper sources in China? Findings from the ITC China Survey.
Tob Control
PUBLISHED: 09-27-2013
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The availability of cigarettes from cheaper sources constitutes a major challenge to public health throughout the world, including China, because it may counteract price-based tobacco control policies. The goal of this study was to identify factors associated with purchasing cigarettes from cheaper sources among adult smokers in China.
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Fluconazole assists berberine to kill fluconazole-resistant Candida albicans.
Antimicrob. Agents Chemother.
PUBLISHED: 09-23-2013
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It was found in our previous study that berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. The aim of the present study was to clarify how BBR and FLC worked synergistically and the underlying mechanism. Antifungal time-kill curves indicated that the synergistic effect of the two drugs was BBR dose dependent rather than FLC dose dependent. In addition, we found that BBR accumulated in C. albicans cells, especially in the nucleus, and resulted in cell cycle arrest and significant change in the transcription of cell cycle-related genes. Besides BBR, other DNA intercalators, including methylene blue, sanguinarine, and acridine orange, were all found to synergize with FLC against FLC-resistant C. albicans. Detection of intracellular BBR accumulation by fluorescence measurement showed that FLC played a role in increasing intracellular BBR concentration, probably due to its effect in disrupting the fungal cell membrane. Similar to the case with FLC, other antifungal agents acting on the cell membrane were able to synergize with BBR. Interestingly, we found that the efflux of intracellular BBR was FLC independent but strongly glucose dependent and associated with the drug efflux pump Cdr2p. These results suggest that BBR plays a major antifungal role in the synergism of FLC and BBR, while FLC plays a role in increasing the intracellular BBR concentration.
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Chinese smokers cigarette purchase behaviours, cigarette prices and consumption: findings from the ITC China Survey.
Tob Control
PUBLISHED: 09-18-2013
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While cigarette purchasing behaviour has been shown to be linked with certain tobacco use outcomes such as quit intentions and quit attempts, there have been very few studies examining cigarette purchasing behaviours and their impact on cigarette price and consumption in China, the worlds largest cigarette consumer.
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Synthesis of an S(T) = 7 [Mn3] mixed-valence complex based on 1,3-propanediol ligand derivatives and its one-dimensional assemblies.
Inorg Chem
PUBLISHED: 09-12-2013
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Controlled organization of high-spin complexes and single-molecule magnets is a great challenge in molecular magnetism in order to study the effect of the intercomplex magnetic interactions on the intrinsic properties of a given magnetic object. In this work, a new S(T) = 7 trinuclear mixed-valence Mn complex, [Mn(III)Mn(II)2(LA)2(Br)4(CH3OH)6] ·Br·(CH3OH)(1.5)·(H2O)(0.5) (1), is reported using a pyridinium-functionalized 1,3-propanediol ligand (H2L(A)Br = 1-(3-bromo-2,2-bis(hydroxymethyl)propyl)pyridinium bromide). Using azido anions as bridging ligands and different pyridinium-functionalized 1,3-propanediol ligands (H2L(B)Br = 1-(3-bromo-2,2-bis(hydroxymethyl)propyl)-4-picolinium bromide; H2L(C)Br = 1-(3-bromo-2,2-bis(hydroxymethyl)propyl)-3,5-lutidinium bromide), the linear [Mn(III)Mn(II)2L2X4](+) building block has been assembled into one-dimensional coordination networks: [Mn(III)Mn(II)2(LA)2(Br)4(CH3OH)4(N3)]·((C2H5)2O)1.25 (2?), [Mn(III)Mn(II)2(L(B))2(Br)4(C2H5OH)(CH3OH)(H2O)2(N3)]·(H2O)0.25 (3?), and [Mn(III)Mn(II)2(L(C))2(Cl)(3.8)(Br)(0.2)(C2H5OH)3(CH3OH)(N3)] (4?). The syntheses, characterization, crystal structures, and magnetic properties of these new [Mn3]-based materials are reported.
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Transurethral Incision of the bladder neck improves voiding efficiency in female patients with detrusor underactivity.
Int Urogynecol J
PUBLISHED: 09-04-2013
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Detrusor underactivity (DU) is a common urologic problem and usually presents with urine retention or large postvoid residual (PVR). Medical treatment of DU does not always achieve satisfactory results. We report the surgical outcomes of transurethral incision of the bladder neck (TUI-BN) in women with DU and urine retention.
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Using Galleria mellonella-Candida albicans infection model to evaluate antifungal agents.
Biol. Pharm. Bull.
PUBLISHED: 09-03-2013
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Candida albicans is the most common fungal pathogen. Galleria mellonella is widely used as an infection model host. Nevertheless, the G. mellonella-C. albicans infection model had not been optimized for drug evaluation before this study. In this work, we revealed that 5 × 10(5) colony forming unit (CFU)/larva was a suitable inoculum to optimize the G. mellonella-C. albicans infection model in order to evaluate antifungal agents. Using our optimized model, the antifungal effect of fluconazole, amphotericin B and flucytosine, and the synergy between amphotericin B and flucytosine were successfully verified. Thus, this study provides a rapid, inexpensive and reliable way to evaluate antifungals in vivo.
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Increased apoptosis and suburothelial inflammation in patients with ketamine-related cystitis: a comparison with non-ulcerative interstitial cystitis and controls.
BJU Int.
PUBLISHED: 08-13-2013
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To investigate the suburothelial inflammation and urothelial dysfunction that occurs with ketamine-related cystitis (KC) and interstitial cystitis/bladder pain syndrome (IC/BPS).
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One-pot synthesis of multicolor MnSe:ZnSe nanocrystals for optical coding.
J Colloid Interface Sci
PUBLISHED: 07-18-2013
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Though the investigation on controlling the fluorescence properties of nanocrystals (NCs) with single emission has been widely reported, few efforts were spent on adjusting the fluorescence properties of NCs with multiple emission peaks. In this work, we successfully synthesized multicolor MnSe:ZnSe NCs with multiple emission peaks and developed a simple and accurate method to realize photoluminescence (PL) spectra (or color) adjustment. The PL of MnSe:ZnSe NCs has two distinct emission peaks, the trap emission of ZnSe at 475nm and Mn(2+)-induced emission at 585nm. By adjusting the nucleation temperature, the emission color of the NCs can be encoded according to the ratio of the emission intensities at 475 and 585nm. With the nucleation temperature rising from 0 to 70°C, the PL ratio between trap emission and Mn(2+)-induced emission can be consecutively changed from (1, 3) to (1, 0.5). In addition, the trap state is deeply inside the NCs rather than on NCs surface so that the trap emission is stable during environment change. Thus, these MnSe:ZnSe NCs hold great promise as novel single-particle coding labels for biomedical imaging.
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The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology.
Cancer Res.
PUBLISHED: 07-15-2013
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The NCI-60 cell lines are the most frequently studied human tumor cell lines in cancer research. This panel has generated the most extensive cancer pharmacology database worldwide. In addition, these cell lines have been intensely investigated, providing a unique platform for hypothesis-driven research focused on enhancing our understanding of tumor biology. Here, we report a comprehensive analysis of coding variants in the NCI-60 panel of cell lines identified by whole exome sequencing, providing a list of possible cancer specific variants for the community. Furthermore, we identify pharmacogenomic correlations between specific variants in genes such as TP53, BRAF, ERBBs, and ATAD5 and anticancer agents such as nutlin, vemurafenib, erlotinib, and bleomycin showing one of many ways the data could be used to validate and generate novel hypotheses for further investigation. As new cancer genes are identified through large-scale sequencing studies, the data presented here for the NCI-60 will be an invaluable resource for identifying cell lines with mutations in such genes for hypothesis-driven research. To enhance the utility of the data for the greater research community, the genomic variants are freely available in different formats and from multiple sources including the CellMiner and Ingenuity websites.
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C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection.
Immunity
PUBLISHED: 05-23-2013
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C-type lectin receptors (CLRs) play critical roles as pattern-recognition receptors (PRRs) for sensing Candida albicans infection, which can be life-threatening for immunocompromised individuals. Here we have shown that Dectin-3 (also called CLECSF8, MCL, or Clec4d), a previously uncharacterized CLR, recognized ?-mannans on the surfaces of C. albicans hyphae and induced NF-?B activation. Mice with either blockade or genetically deleted Dectin-3 were highly susceptible to C. albicans infection. Dectin-3 constantly formed heterodimers with Dectin-2, a well-characterized CLR, for recognizing C. albicans hyphae. Compared to their respective homodimers, Dectin-3 and Dectin-2 heterodimers bound ?-mannans more effectively, leading to potent inflammatory responses against fungal infections. Together, our study demonstrates that Dectin-3 forms a heterodimeric PRR with Dectin-2 for sensing fungal infection and suggests that different CLRs may form different hetero- and homodimers, which provide different sensitivity and diversity for host cells to detect various microbial infections.
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The effect of cigarette prices on brand-switching in China: a longitudinal analysis of data from the ITC China survey.
Tob Control
PUBLISHED: 05-22-2013
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Recent studies have found that Chinese smokers are relatively unresponsive to cigarette prices. As the Chinese government contemplates higher tobacco taxes, it is important to understand the reasons for this low response. One possible explanation is that smokers buffer themselves from rising cigarette prices by switching to cheaper cigarette brands.
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Carbonate-mediated Fe(II) oxidation in the air-cathode fuel cell: a kinetic model in terms of Fe(II) speciation.
J Phys Chem A
PUBLISHED: 05-22-2013
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Due to the high redox activity of Fe(II) and its abundance in natural waters, the electro-oxidation of Fe(II) can be found in many air-cathode fuel cell systems, such as acid mine drainage fuel cells and sediment microbial fuel cells. To deeply understand these iron-related systems, it is essential to elucidate the kinetics and mechanisms involved in the electro-oxidation of Fe(II). This work aims to develop a kinetic model that adequately describes the electro-oxidation process of Fe(II) in air-cathode fuel cells. The speciation of Fe(II) is incorporated into the model, and contributions of individual Fe(II) species to the overall Fe(II) oxidation rate are quantitatively evaluated. The results show that the kinetic model can accurately predict the electro-oxidation rate of Fe(II) in air-cathode fuel cells. FeCO3, Fe(OH)2, and Fe(CO3)2(2-) are the most important species determining the electro-oxidation kinetics of Fe(II). The Fe(II) oxidation rate is primarily controlled by the oxidation of FeCO3 species at low pH, whereas at high pH Fe(OH)2 and Fe(CO3)2(2-) are the dominant species. Solution pH, carbonate concentration, and solution salinity are able to influence the electro-oxidation kinetics of Fe(II) through changing both distribution and kinetic activity of Fe(II) species.
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Multicenter research on the BACTEC MGIT 960 system for the second-line drugs susceptibility testing of Mycobacterium tuberculosis in China.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 05-20-2013
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The reliability of the BACTEC MGIT 960 system for the second-line drugs (capreomycin [CPM], kanamycin [KAN], ofloxacin [OFX] and ethionamide [ETH]) susceptibility testing (DST) of Mycobacterium tuberculosis (M. tuberculosis) was compared to that of traditional Lowenstein-Jensen (L-J) proportion method (PM) among four different sites in China. After resolution of discrepant results by retesting the strains using both methods in the National Reference Laboratory of tuberculosis, the overall concordance values between the 2 systems were 99.7% (kappa value: 0.97) for CPM, 99.7% (kappa value: 0.97) for KAN, 100.0% (kappa value: 1.00) for OFX, and 98.6% (kappa value: 0.95) for ETH. The average turnaround time with BACTEC MGIT 960 system among four sites was 8.9 ± 1.7 days, significantly shorter than 28 days with the traditional L-J PM. Therefore, the BACTEC MGIT 960 system is a reliable and rapid method for the second-line drug susceptibility testing of tuberculosis in China. Notably, a stricter quality control program should be routinely carried out when clinical laboratories perform the second-line DST with BACTEC MGIT 960 system.
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A metabolomics-driven elucidation of the anti-obesity mechanisms of xanthohumol.
J. Biol. Chem.
PUBLISHED: 05-14-2013
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Mild, mitochondrial uncoupling increases energy expenditure and can reduce the generation of reactive oxygen species (ROS). Activation of cellular, adaptive stress response pathways can result in an enhanced capacity to reduce oxidative damage. Together, these strategies target energy imbalance and oxidative stress, both underlying factors of obesity and related conditions such as type 2 diabetes. Here we describe a metabolomics-driven effort to uncover the anti-obesity mechanism(s) of xanthohumol (XN), a prenylated flavonoid from hops. Metabolomics analysis of fasting plasma from obese, Zucker rats treated with XN revealed decreases in products of dysfunctional fatty acid oxidation and ROS, prompting us to explore the effects of XN on muscle cell bioenergetics. At low micromolar concentrations, XN acutely increased uncoupled respiration in several different cell types, including myocytes. Tetrahydroxanthohumol also increased respiration, suggesting electrophilicity did not play a role. At higher concentrations, XN inhibited respiration in a ROS-dependent manner. In myocytes, time course metabolomics revealed acute activation of glutathione recycling and long term induction of glutathione synthesis as well as several other changes indicative of short term elevated cellular stress and a concerted adaptive response. Based on these findings, we hypothesize that XN may ameliorate metabolic syndrome, at least in part, through mitochondrial uncoupling and stress response induction. In addition, time course metabolomics appears to be an effective strategy for uncovering metabolic events that occur during a stress response.
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Synthesis and one-pot tethering of hydroxyl-capped phosphorylcholine onto cellulose membrane for improving hemocompatibility and antibiofouling property.
Colloids Surf B Biointerfaces
PUBLISHED: 04-23-2013
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Tethering of biomimetic phosphorylcholine derivative onto the surface of biomedical devices is an effective method for improving hemocompatibility and antibiofouling property. Herein, series of novel hydroxyl-capped phosphorylcholines (HOPC) with different carbon spacer lengths were first synthesized and characterized with element analysis (EA), Fourier transform infrared spectroscopy(FTIR), and nuclear magnetic resonance spectroscopy (NMR). Then, HOPC (n=5, 2a) was one-pot tethered onto cellulose membrane with hexamethylene diisocyanate (HDI) as a coupling agent. The existence of phosphorylcholine was demonstrated by water contact angle measurement, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). The hemocompatibility and antibiofouling property were evaluated by hemolytic test, platelet adhesion, protein adsorption, and Escherichia coli adhesion test. The results showed that cellulose membranes tethered with HOPC exhibited excellent hemocompatibility featured by low platelet adhesion and ?brinogen adsorption as well as antibiofouling property with bacterial adhesion resistance.
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Utility of insects for studying human pathogens and evaluating new antimicrobial agents.
Adv. Biochem. Eng. Biotechnol.
PUBLISHED: 04-23-2013
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Insect models, such as Galleria mellonella and Drosophila melanogaster have significant ethical, logistical, and economic advantages over mammalian models for the studies of infectious diseases. Using these models, various pathogenic microbes have been studied and many novel virulence genes have been identified. Notably, because insects are susceptible to a wide variety of human pathogens and have immune responses similar to those of mammals, they offer the opportunity to understand innate immune responses against human pathogens better. It is important to note that insect pathosystems have also offered a simple strategy to evaluate the efficacy and toxicity of many antimicrobial agents. Overall, insect models provide a rapid, inexpensive, and reliable way as complementary hosts to conventional vertebrate animal models to study pathogenesis and antimicrobial agents.
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Fractal H-shaped plasmonic nanocavity.
Nanotechnology
PUBLISHED: 04-19-2013
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Based on complementary fractal geometry structures, we design a novel infrared quasi-three-dimensional (3D) nanocavity with a localized enhanced field with multiband resonant frequencies. The fractals offer the nanostructure two important characteristics, multiband functionality and a subwavelength effect. The electric field, power flow, and the field intensity distributions are given to indicate the internal mechanism of the localized enhanced field in the nanocavity. Additionally, the effective medium method is established to retrieve the permittivity and impedance of the structure. It is shown that a strongly enhanced localized field is achieved in the nanocavity at two different resonant frequencies by using the finite difference time domain method. The field intensity in the nanocavity is enhanced by a factor of up to 60 times over that of the incident light because of the important contribution of the loss factor in the permittivity. The surface plasmon hybridization is thought to play an important role in the strong localized field enhancement. The multiband property and high localized intensity offer the nanocavity great potential for applications in surface enhanced Raman scattering and other nanoscale novel devices.
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Framing effects in medical situations: distinctions of attribute, goal and risky choice frames.
J. Int. Med. Res.
PUBLISHED: 04-18-2013
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To verify whether three different framing effects (risky choice, attribute and goal) exist in simulated medical situations and to analyse any differences.
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Tobacco control challenges in East Asia: proposals for change in the worlds largest epidemic region.
Tob Control
PUBLISHED: 04-17-2013
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East Asia is one of the worlds largest tobacco epidemic regions. Although several international studies have evaluated the status of tobacco control in this region, the findings have not been integrated with knowledge on domestic activities at the national and municipal levels. We analysed the current tobacco control situation in three East Asian countries, Japan, China and the Republic of Korea, using both international and domestic data sources. We collected data between 2008 and 2011 in each country according to the framework of WHOs MPOWER (Monitoring, Protect, Offer, Warn, Enforcement and Raise) approach for guiding implementation of the WHO Framework Convention on Tobacco Control. Analysis revealed that 37-53% of adult men were current smokers and that smoking prevalence among middle-aged men reached 63%. Less than 20% of male smokers plan to quit and the use of nicotine replacement drugs was 14% at maximum. Forty-six percent or more of men and 20% or more of women were exposed to passive smoking at workplaces and at home, respectively. Many tobacco industry activities remain unrestricted and prevalent. Our findings indicate an urgent need for the following set of policies: raise cigarette prices to increase the quit attempt rate, particularly among adult men; develop a multi-component quitting assistance system to provide adequate assistance for smoking cessation; implement effective smoke-free policies in workplaces and public places to reduce exposure to passive smoking; and rebuild the administrative structure to denormalise tobacco industry activities. The importance of these standard approaches should be reaffirmed by all tobacco control policymakers in East Asia.
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