JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Complete sequence analysis of mitochondrial DNA and telomere length in aplastic anemia.
Int. J. Mol. Med.
PUBLISHED: 08-13-2014
Show Abstract
Hide Abstract
The present study was primarily undertaken to examine the hypothesis that mitochondrial DNA (mtDNA) mutations and telomere length may be associated with aplastic anemia (AA). Our study included a single institution analysis of 40 patients presenting with AA first diagnosed at the Affiliated Hospital of Shandong, University of Traditional Chinese Medicine between 2010 and 2013. Bone marrow and oral epithelial samples were collected from patients with AA (n=40) for mtDNA mutation and telomere length determinations. Bone marrow specimens were collected from 40 healthy volunteers as controls for the examination of telomere length. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and the products were used for sequencing and analysis. We detected 146 heteroplasmic mutations in 18 genes from 40 patients with AA, including 39 silent mutations and 28 frameshift mutations. We used the gamma globin gene (HBG) as the control gene in real-time PCR to survey the relative telomere length measurements of the patients with AA and the healthy volunteers. Telomere length was expressed as the relative T/S value. We observed a negative correlation between the mtDNA non-silent mutation and the white blood cell (WBC) count, hemoglobin and platelet count. Of note, there was a positive correlation between the relative T/S value and WBC count, hemoglobin and platelet count, and a negative correlation between the non-silent mutation and the relative T/S value. We conclude that the functional impairment of the mitochondrial respiratory chain induced by mutation and telomere length shortening may play an important role in the process of hematopoietic failure in patients with AA. Additionally, mtDNA mutations and telomere length shortening influenced each other.
Related JoVE Video
Focal Adhesion Kinase Knockdown in Carcinoma-Associated Fibroblasts Inhibits Oral Squamous Cell Carcinoma Metastasis via Downregulating MCP-1/CCL2 Expression.
J. Biochem. Mol. Toxicol.
PUBLISHED: 06-23-2014
Show Abstract
Hide Abstract
Carcinoma-associated fibroblasts (CAFs) have been demonstrated to play an important role in the occurrence and development of oral squamous cell carcinoma (OSCC). The aim of this study is to investigate the influence of CAFs on OSCC cells and to explore the role of focal adhesion kinase (FAK) in this process. The results showed that oral CAFs expressed a higher level of FAK than normal human gingival fibroblasts (HGFs), and the conditioned medium (CM) of CAFs could induce the invasion and migration of SCC-25, one oral squamous carcinoma cell line. However, knockdown of FAK by small interfering RNA (siRNA) resulted in inhibition of CAF-CM induced cell invasion and migration in SCC-25, probably by reducing the production of monocyte chemoattractant protein-1 (MCP-1/CCL2), one of downstream target chemokines. Therefore, our findings indicated that targeting FAK in CAFs might be a promising strategy for the treatment of OSCC in the future.
Related JoVE Video
Study of N-isopropoxypropyl-N'-ethoxycarbonyl thiourea adsorption on chalcopyrite using in situ SECM, ToF-SIMS and XPS.
J Colloid Interface Sci
PUBLISHED: 06-22-2014
Show Abstract
Hide Abstract
In situ scanning electrochemical microscopy (SECM) was used to study N-isopropoxypropyl-N'-ethoxycarbonyl thiourea (iPOPECTU) adsorption on chalcopyrite. The in situ SECM images indicated a preferential adsorption of iPOPECTU on chalcopyrite surfaces, resulting in a decrease in the probing electrochemical current response. The surfaces after iPOPECTU adsorption were analyzed by time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). ToF-SIMS results provided a strong evidence of iPOPECTU binding with copper only. XPS analysis showed the reduction of cupric to cuprous on chalcopyrite surfaces as a result of iPOPECTU adsorption. Our results shed light on adsorption mechanism of iPOPECTU on the surface of chalcopyrite samples.
Related JoVE Video
Two new spirooxindole alkaloids from rhizosphere strain Streptomyces sp. xzqh-9.
Bioorg. Med. Chem. Lett.
PUBLISHED: 06-02-2014
Show Abstract
Hide Abstract
Two new spirooxindole alkaloids spindomycins A (1) and B (2) were isolated from rhizosphere strain Streptomyces sp. xzqh-9. Their structures were elucidated by comprehensive spectroscopic analyses of NMR and MS data. The absolute configurations of 1 and 2 were determined by experimental and theoretical calculation of electronic circular dichroism (ECD). Antitumor, lactate dehydrogenase, and tyrosine kinase inhibitory activities of two compounds were evaluated, while only spindomycin B (2) exhibited weak inhibitory activity against tyrosine kinase Bcr-Abl.
Related JoVE Video
Embedded carbon nanotubes nanoparticles in plasma membrane induce cellular calcium outflow imbalancing.
J Nanosci Nanotechnol
PUBLISHED: 04-18-2014
Show Abstract
Hide Abstract
In this report, embedded single-wall carbon nanotubes (SWCNTs) nanoparticles in plasma membrane inducing cellular calcium outflow imbalancing are disclosed. Compared ssDNA-SWCNTs with polystyrene (PS) nanoparticles, we analyzed the cytotoxicity of these nanoparticles and the effect of these nanoparticles on intracellular Ca2+ ion levels by depletion of Ca2+ from the endoplasmic reticulum (ER) evoked by Thapsigargin (Tg) in SKN-SH cells. The results had shown that ssDNA-SWCNTs and PS nanoparticles have no cytotoxicity on SKN-SH cells. However, contrary to PS nanoparticles, cellular Ca2+ ion outflow imbalancing was investigated in SKN-SH cells after pretreated with ssDNA-SWCNTs induced by Tg, which could be proposed mainly due to the interaction of embedded ssDNA-SWCNTs with cellular membrane.
Related JoVE Video
Efficient expression of functional (?6?2)2?3 AChRs in Xenopus oocytes from free subunits using slightly modified ?6 subunits.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Human (?6?2)(?4?2)?3 nicotinic acetylcholine receptors (AChRs) are essential for addiction to nicotine and a target for drug development for smoking cessation. Expressing this complex AChR is difficult, but has been achieved using subunit concatamers. In order to determine what limits expression of ?6* AChRs and to efficiently express ?6* AChRs using free subunits, we investigated expression of the simpler (?6?2)2?3 AChR. The concatameric form of this AChR assembles well, but is transported to the cell surface inefficiently. Various chimeras of ?6 with the closely related ?3 subunit increased expression efficiency with free subunits and produced pharmacologically equivalent functional AChRs. A chimera in which the large cytoplasmic domain of ?6 was replaced with that of ?3 increased assembly with ?2 subunits and transport of AChRs to the oocyte surface. Another chimera replacing the unique methionine 211 of ?6 with leucine found at this position in transmembrane domain 1 of ?3 and other ? subunits increased assembly of mature subunits containing ?3 subunits within oocytes. Combining both ?3 sequences in an ?6 chimera increased expression of functional (?6?2)2?3 AChRs to 12-fold more than with concatamers. This is pragmatically useful, and provides insights on features of ?6 subunit structure that limit its expression in transfected cells.
Related JoVE Video
Clinical characteristics and immunogenetics of BCGosis/BCGitis in Chinese children: a 6 year follow-up study.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
In this study, the clinical and immunogenetical features in a cohort of Chinese patients with BCGosis/BCGitis were investigated. For the patients with abnormal immunological functions, Sanger sequencing was used to identify the involved genes. There were 74 confirmed cases of BCGosis/BCGitis during 2007-2012. Classified by infected tissues and organs, no cases only had local infection, 39 patients had a regional infection, 21 patients had a distant infection and 14 patients had a disseminated infection. Thirty-two patients (43.2%) had definitive primary immunodeficiency diseases (PID) and chronic granulomatous disease (CGD) is the most common PID (n?=?23, accounted for 71.9% of all PID patients). For CGD patients, based on the anti-tuberculosis treatment, administration of rhIFN-? resulted in better control of BCGosis/BCGitis. The results indicate that PIDs are associated with susceptibility to BCG disease. For children with BCGosis/BCGitis, immune function evaluation is necessary, and IFN-? treatment for BCGosis/BCGitis patients with CGD is effective.
Related JoVE Video
Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for ?4?2?5 nicotinic acetylcholine receptors.
Bioorg. Med. Chem. Lett.
PUBLISHED: 09-04-2013
Show Abstract
Hide Abstract
The design and synthesis of a series of substituted heteroaromatic ?4?2?5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2-yl)benzonitrile (5k) and 3,3-(2H-tetrazole-2,5-diyl)dipyridine (12h) with good in vitro efficacy were discovered.
Related JoVE Video
Pemetrexed plus platinum or gemcitabine plus platinum for advanced non-small cell lung cancer: final survival analysis from a multicentre randomized phase II trial in the East Asia region and a meta-analysis.
Respirology
PUBLISHED: 06-29-2013
Show Abstract
Hide Abstract
Pemetrexed plus platinum has shown efficacy as a first-line treatment for advanced non-small cell lung cancer (NSCLC), but little is known about its efficacy and safety in East Asian patients. We report the final analysis of overall survival (OS) from a multicentre, randomized, phase II trial in chemotherapy-naive Chinese patients with advanced NSCLC. An additional meta-analysis was performed to systematically evaluate pemetrexed/platinum as first-line treatment for advanced NSCLC.
Related JoVE Video
Genetic regulation and potentially therapeutic application of cancer-associated fibroblasts in oral cancer.
J. Oral Pathol. Med.
PUBLISHED: 05-16-2013
Show Abstract
Hide Abstract
Carcinoma-associated fibroblast (CAF) is the most important host cell type in tumor microenvironment, which greatly contributes to tumor initiation, progression, and metastasis. Therefore, a large amount of data has emerged, showing the cancer-promoting function of these cells via paracrine effects that escort tumor cells through all the steps of cancer development. CAF is a heterogeneous cell population that can arise from the differentiation of resting fibroblasts, epithelial cells, endothelial cells, and mesenchymal stem cells. This review summarizes the current knowledge of the role of CAFs in tumor progression, with a particular focus on the cellular and molecular features and recent advances in researches on the genetic status and microRNA regulation, and addresses the potential prognostic and therapeutic values for patients with oral cancer by targeting CAFs.
Related JoVE Video
Development of pineapple microsatellite markers and germplasm genetic diversity analysis.
Biomed Res Int
PUBLISHED: 04-29-2013
Show Abstract
Hide Abstract
Two methods were used to develop pineapple microsatellite markers. Genomic library-based SSR development: using selectively amplified microsatellite assay, 86 sequences were generated from pineapple genomic library. 91 (96.8%) of the 94 Simple Sequence Repeat (SSR) loci were dinucleotide repeats (39 AC/GT repeats and 52 GA/TC repeats, accounting for 42.9% and 57.1%, resp.), and the other three were mononucleotide repeats. Thirty-six pairs of SSR primers were designed; 24 of them generated clear bands of expected sizes, and 13 of them showed polymorphism. EST-based SSR development: 5659 pineapple EST sequences obtained from NCBI were analyzed; among 1397 nonredundant EST sequences, 843 were found containing 1110 SSR loci (217 of them contained more than one SSR locus). Frequency of SSRs in pineapple EST sequences is 1SSR/3.73 kb, and 44 types were found. Mononucleotide, dinucleotide, and trinucleotide repeats dominate, accounting for 95.6% in total. AG/CT and AGC/GCT were the dominant type of dinucleotide and trinucleotide repeats, accounting for 83.5% and 24.1%, respectively. Thirty pairs of primers were designed for each of randomly selected 30 sequences; 26 of them generated clear and reproducible bands, and 22 of them showed polymorphism. Eighteen pairs of primers obtained by the one or the other of the two methods above that showed polymorphism were selected to carry out germplasm genetic diversity analysis for 48 breeds of pineapple; similarity coefficients of these breeds were between 0.59 and 1.00, and they can be divided into four groups accordingly. Amplification products of five SSR markers were extracted and sequenced, corresponding repeat loci were found and locus mutations are mainly in copy number of repeats and base mutations in the flanking region.
Related JoVE Video
Dual detection strategy for electrochemical analysis of glucose and nitrite using a partitionally modified electrode.
Analyst
PUBLISHED: 11-07-2011
Show Abstract
Hide Abstract
A dual-region modified electrode was designed and fabricated by means of partitioned electrodeposition of gold and platinum nanoparticles on an indium tin oxide (ITO) conductive glass for dual-component electrochemical detection. The two differently modified regions were assigned to detect two analytes, separately and simultaneously. The gold nanoparticle modified ITO region (AuNPs/ITO) was used for glucose detection while the platinum nanoparticle modified ITO region (PtNPs/ITO) for nitrite detection. The glucose oxidation peak current at 0.10 V on AuNPs/ITO exhibited a linear dependence on the concentration of glucose and was used to determine the concentration of glucose in dual-detection. The nitrite reduction peak current at PtNPs/ITO showed a nonlinear dependence on the concentration of nitrite. A theoretical model combining the adsorption-controlled and the mass-transfer-controlled kinetics was proposed to quantitatively describe the nonlinear behavior. Though the presence of glucose interfered with the electrochemical detection of nitrite, it was demonstrated that the influence of glucose on nitrite detection can be corrected. On the basis of the proposed theoretical model, the simultaneous dual-detection of glucose and nitrite was accomplished at ITO electrodes partitionally modified with AuNPs and PtNPs.
Related JoVE Video
Investigation of the molecular mechanism of the ?7 nicotinic acetylcholine receptor positive allosteric modulator PNU-120596 provides evidence for two distinct desensitized states.
Mol. Pharmacol.
PUBLISHED: 09-01-2011
Show Abstract
Hide Abstract
Although ?7 nicotinic acetylcholine receptors are considered potentially important therapeutic targets, the development of selective agonists has been stymied by the ?7 receptors intrinsically low probability of opening (P(open)) and the concern that an agonist-based therapeutic approach would disrupt endogenous cholinergic function. Development of ?7 positive allosteric modulators (PAMs) holds promise of avoiding both issues. N-(5-Chloro-2,4-dimethoxyphenyl)-N-(5-methyl-3-isoxazolyl)-urea (PNU-120596) is one of the most effective ?7 PAMs, with a mechanism associated, at least in part, with the destabilization of desensitized states. We studied the mechanism of PNU-120596 potentiation of ?7 receptors expressed in Xenopus laevis oocytes and outside-out patches from BOSC 23 cells. We identify two forms of ?7 desensitization: one is destabilized by PNU-120596 (D(s)), and the other is induced by strong episodes of activation and is stable in the presence of the PAM (D(i)). Our characterization of prolonged bursts of single-channel currents that occur with PNU-120596 provide a remarkable contrast to the behavior of the channels in the absence of the PAM. Individual channels that avoid the D(i) state show a 100,000-fold increase in P(open) compared with receptors in the nonpotentiated state. In the presence of PNU-120596, balance between D(s) and D(i) is dynamically regulated by both agonist and PAM binding, with maximal ion channel activity at intermediate levels of binding to both classes of sites. In the presence of high agonist concentrations, competitive antagonists may have the effect of shifting the balance in favor of D(s) and increasing ion channel currents.
Related JoVE Video
Evaluation of optical clearing with the combined liquid paraffin and glycerol mixture.
Biomed Opt Express
PUBLISHED: 05-11-2011
Show Abstract
Hide Abstract
By scanning biological tissues in vivo and in vitro with optical coherence tomography, it is found that liquid paraffin can enhance the percutaneous penetration of glycerol in deep layers of tissue and take synergistically optical clearing effect with glycerol. It is shown from experimental results that 30% - 50% liquid paraffin glycerol solutions have the best enhancement effect. Considering the refractive index of liquid paraffin and its medicinal value, we think liquid paraffin will play an important role in optical clearing as the penetration enhancer of glycerol in future clinical research.
Related JoVE Video
Nerves of the mediastinum.
Thorac Surg Clin
PUBLISHED: 04-12-2011
Show Abstract
Hide Abstract
Knowledge of the anatomy of the mediastinal nerves is essential for the evaluation and surgical treatment of most thoracic neoplasms. Thorough knowledge of the normal anatomy of the mediastinal nerves and of their variants cannot be overestimated because nerve trauma during nerve anatomy is also important because mediastinal or lung tumors can locally infiltrate those nerves either directly or through nodal metastases, making them generally unresectable.
Related JoVE Video
Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.
Biochem. Pharmacol.
PUBLISHED: 03-21-2011
Show Abstract
Hide Abstract
Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (agonists, partial agonists, competitive antagonists) at conventional agonist binding sites, but is also regulated in either negative or positive ways by the binding of ligands to other modulatory sites. In this review, we discuss models for the activation and desensitization of nAChR, and the discovery of multiple types of ligands that influence those processes in both heteromeric nAChR, such as the high-affinity nicotine receptors of the brain, and homomeric ?7-type receptors. In recent years, ?7 nAChRs have been identified as a potential target for therapeutic indications leading to the development of ?7-selective agonists and partial agonists. However, unique properties of ?7 nAChR, including low probability of channel opening and rapid desensitization, may limit the therapeutic usefulness of ligands binding exclusively to conventional agonist binding sites. New enthusiasm for the therapeutic targeting of ?7 has come from the identification of ?7-selective positive allosteric modulators (PAMs) that work effectively on the intrinsic factors that limit ?7 ion channel activation. While these new drugs appear promising for therapeutic development, we also consider potential caveats and possible limitations for their use, including PAM-insensitive forms of desensitization and cytotoxicity issues.
Related JoVE Video
Effect of N-linked glycosylation on secretion and activity of recombinant DSPAalpha1 expressed in Pichia pastoris.
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 12-15-2010
Show Abstract
Hide Abstract
The thrombolytic agent DSPAalpha1 is currently undergoing clinical trials for the treatment of acute ischemic stroke and has shown good pharmacodynamic, pharmacokinetic and safety profiles. Here, the DSPAalpha1 gene, optimized for the preferred codons of yeast, was cloned into the Pichia pastoris strains GS115 and KM71. Both expression systems produced functional DSPAalpha1 into the broth medium under shaking flask growth conditions with the yield of about 70 mg/L, and 105 mg/L, respectively. In addition, three glycosylation minus DSPAalpha1 mutants, constructed by site-directed mutagenesis, were also expressed in Pichia pastoris. The mutant proteins were assayed by SDS-PAGE and fibrin degradation activities were evaluated. The secretion levels of all the mutants, especially N362Q and N117Q/N362Q, were so lower compared to the wild-type DSPAalpha1 that only minimal quantities of mutant protein could be recovered by purification from the culture medium. The protein specific activities from mutants (N117Q, N362Q) were less 25% than that of the wild type protein. These results imply that the N-linked carbohydrate chains (at N117 and N362) are vital for the enzymatic activity of rDSPAalpha1 and for its secretion from Pichia pastoris.
Related JoVE Video
Tethered agonist analogs as site-specific probes for domains of the human ?7 nicotinic acetylcholine receptor that differentially regulate activation and desensitization.
Mol. Pharmacol.
PUBLISHED: 09-07-2010
Show Abstract
Hide Abstract
Homomeric ?7 nicotinic acetylcholine receptors represent an important and complex pharmaceutical target. They can be activated by structurally diverse agonists and are highly likely to enter and remain in desensitized states at rates determined by the structures of the agonists. To identify structural elements regulating this function, we introduced reactive cysteines into the ?7 ligand-binding domain allowing us to bind sulfhydryl-reactive (SH) agonist analogs or control reagents onto specific positions in the ligand binding domain. We identified four ?7 mutants (S36C, L38C, W55C, and L119C) in which the tethering of the SH reagents blocked further acetylcholine-evoked activation of the receptor. However, after selective reaction with SH agonist analogs, the type II allosteric modulator N-(5-chloro-2,4-dimethoxyphenyl)-N-(5-methyl-3-isoxazolyl-3-isoxazolyl)-urea (PNU-120596) could reactivate L119C and W55C mutants and receptors with a reduced or modified C-loop. Modified S36C and L38C mutants were insensitive to reactivation by PNU-120596, whether they were reacted with agonist analogs or alternative SH reagents. Molecular modeling showed that in the W55C and L119C mutants, the ammonium pharmacophore of the agonist analog methanethiosulfonate-ethyltrimethylammonium would be in a similar but nonidentical position underneath the C-loop. The orientation assumed by the ligand tethered to 119C was approximately 3-fold more sensitive to PNU-120596 than the alternative pose at 55C. Our results support the hypothesis that a single ligand can bind within the receptor in different ways and, depending on the specific binding pose, may variously promote activation or desensitization, or, alternatively, function as a competitive antagonist. This insight may provide a new approach for drug development.
Related JoVE Video
Cysteine accessibility analysis of the human alpha7 nicotinic acetylcholine receptor ligand-binding domain identifies L119 as a gatekeeper.
Neuropharmacology
PUBLISHED: 04-16-2010
Show Abstract
Hide Abstract
A large number of structurally diverse ligands have been produced to selectively target ?7 nicotinic acetylcholine receptors (nAChRs). We applied the method of scanning cysteine accessibility mutations (SCAM) to the ligand-binding domain of the ?7 nAChR to identify subdomains of particular importance to the binding and subsequent activation by select agonists. We evaluated the activity of four structurally distinct ?7 agonists on wild-type human ?7 and 44 targeted mutants expressed in Xenopus oocytes. Responses were measured prior and subsequent to the application of the sulfhydryl reagent methanethiosulfonate ethylammonium (MTSEA). One mutant (C116S) served as a Cys-null control, and the additional mutants were made in the C116S background. In many cases, the insertion of free cysteines into the agonist-binding site had a negative effect on function, with 12 of 44 mutants showing no detectable responses to ACh, and with only 19 of the 44 mutants showing sufficiently large responses to permit further study. Several of the cysteine mutations, including W55C, showed selectively reduced responses to the largest agonist tested, 2-methoxy,4-hydroxy-benzylidene anabaseine. Interestingly, although homology models suggest that most of the introduced cysteine mutations should have had good solvent accessibility, application of MTSEA had no effect or produced only modest changes in the agonist response profile of most mutants. Consistent with previous studies implicating W55 to play important roles in agonist activation, MTSEA treatment further decreased the functional responses of W55C to all the test agonists. While the cysteine mutation at L119 itself had relatively little effect on receptor function, treatment of L119C receptors with MTSEA or alternative cationic sulfhydryl reagents profoundly decreased activation by all agonists tested, suggesting a general block of gating. The homologous mutation in heteromeric nAChRs produced similar results, provided that the mutation was placed in the beta subunit complementary surface of the ligand-binding domain. Structural models locate the L119 residue directly across the subunit interface from the C-loop of the primary face of the binding domain. Our data suggest that a covalent modification of L119C by MTSEA or other cationic reagents might block the binding of even small agonists such as TMA through electrostatic interactions. Reaction of L119C with small non-polar reagents increases activation by small agonists but can block the access of large ligands such as benzylidene anabaseines to the ligand-binding domain.
Related JoVE Video
Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China.
J. Clin. Immunol.
PUBLISHED: 08-18-2009
Show Abstract
Hide Abstract
X-Linked agammaglobulinemia is a prototypical humoral immunodeficiency with the mutation of the Brutons tyrosine kinase gene.
Related JoVE Video
Pollution assessment and source identifications of polycyclic aromatic hydrocarbons in sediments of the Yellow River Delta, a newly born wetland in China.
Environ Monit Assess
PUBLISHED: 05-21-2009
Show Abstract
Hide Abstract
The levels and possible sources of 16 priority polycyclic aromatic carbons (PAHs) in the sediments from the Yellow River Delta (YRD) were investigated. The total PAH concentrations ranged from 23.9 to 520.6 microg kg(-1) with a mean value of 150.9 microg kg(-1), indicating low or medium levels compared with reported values of other deltas. The concentrations of the 16 individual PAHs presented varied profiles among different regions. The ecological risk assessment of PAHs showed that adverse effects would rarely occur in the sediments of the YRD based on the effect range-low quotients and the probability risk assessment. The PAH compositions and the principal component analysis (PCA) with multiple linear regression (MLR) uniformly presumed the mixed sources of pyrogenic- and petrogenic-deriving PAHs in the YRD. By PCA with MLR, the contributions of major sources were quantified as 36.4% from oil burning, 33.1% from biomass combustion, and 30.5% from diesel emission sources.
Related JoVE Video
Synthesis of H-bonding probes of alpha7 nAChR agonist selectivity.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-03-2009
Show Abstract
Hide Abstract
The alpha7 subtype of the nicotinic acetylcholine receptor (nAChR) is the target of studies aimed at identifying features that will lead to the development of selective therapeutics. Five arylidine anabaseines, three with pyridine rings and two with the pyrrole rings, were synthesized in 35-65% yield via aldol condensation. The compounds are homologs of benzylidine anabaseine and were chosen for synthesis because they provide either a hydrogen bond acceptor (pyridines) or hydrogen bond donor (pyrroles) that may interact with the receptor within the benzylidine selectivity motif. Initial analysis of the new compounds at 100 microM concentration reveal that the two pyrrole anabaseines are good partial agonists of the alpha7 nAChR, having 40% of the efficacy of ACh, efficacy comparable to 4OH-GTS-21, and dramatically enhanced efficacy relative to the 2- and 4-pyridinyl compounds. The pyrrole compounds were confirmed to be alpha7 selective, displaying preference for this receptor over muscle and heteromeric neuronal receptor subtypes.
Related JoVE Video
Characterization, ecological risk assessment and source diagnostics of polycyclic aromatic hydrocarbons in water column of the Yellow River Delta, one of the most plenty biodiversity zones in the world.
J. Hazard. Mater.
PUBLISHED: 02-02-2009
Show Abstract
Hide Abstract
As one of the most active regions of land-ocean interaction among the large river deltas in the world, the Yellow River Delta (YRD) gains increasing concern on its ecological and environmental conditions. However, few studies on polycyclic aromatic hydrocarbons (PAHs) have been reported for this area. In this study, the distribution characteristics, probabilistic risk and possible sources of PAHs were investigated in the water column of the YRD. The PAH concentrations were found to be at relatively low or medium levels (121.3 ng L(-1) in water and 209.1n g g(-1) in suspended particulate matter (SPM) on average), and the result of probability risk assessment additionally elucidated low PAH ecological risk in the YRD. The PAH composition showed that low and moderate molecular PAHs were the major species in water phase, whereas the SPM showed a different proportion of each PAH composition. An interesting result was found that low-ring PAHs and salinity in this land-ocean interaction area had a positive relationship (R=0.609). For PAH source identification, both diagnostic ratios of selected PAHs and principal component analysis (PCA) with multiple linear regression (MLR) analysis were studied, suggesting mixed sources of pyrogenic and petrogenic deriving PAHs in the YRD.
Related JoVE Video
Study on application of optical clearing technique in skin diseases.
J Biomed Opt
Show Abstract
Hide Abstract
So far, the study of the optical clearing is almost always about healthy tissue. However, the ultimate goal is to detect diseases for clinical application. Optical clearing on diseased skins is explored. The effect is evaluated by applying a combined liquid paraffin and glycerol mixed solution on several kinds of diseased skins in vitro. Scanning experiments from optical coherence tomography show that it has different effects among fibroma, pigmented nevus, and seborrheic keratosis. Based on the results, we conclude that different skin diseases have different compositions and structures, and their optical parameters and biological characteristics should be different, which implies that the optical clearing technique may have selectivity and may not be suitable for all kinds of skin diseases.
Related JoVE Video
Potential state-selective hydrogen bond formation can modulate activation and desensitization of the ?7 nicotinic acetylcholine receptor.
J. Biol. Chem.
Show Abstract
Hide Abstract
A series of arylidene anabaseines were synthesized to probe the functional impact of hydrogen bonding on human ?7 nicotinic acetylcholine receptor (nAChR) activation and desensitization. The aryl groups were either hydrogen bond acceptors (furans), donors (pyrroles), or neither (thiophenes). These compounds were tested against a series of point mutants of the ligand-binding domain residue Gln-57, a residue hypothesized to be proximate to the aryl group of the bound agonist and a putative hydrogen bonding partner. Q57K, Q57D, Q57E, and Q57L were chosen to remove the dual hydrogen bonding donor/acceptor ability of Gln-57 and replace it with hydrogen bond donating, hydrogen bond accepting, or nonhydrogen bonding ability. Activation of the receptor was compromised with hydrogen bonding mismatches, for example, pairing a pyrrole with Q57K or Q57L, or a furan anabaseine with Q57D or Q57E. Ligand co-applications with the positive allosteric modulator PNU-120596 produced significantly enhanced currents whose degree of enhancement was greater for 2-furans or -pyrroles than for their 3-substituted isomers, whereas the nonhydrogen bonding thiophenes failed to show this correlation. Interestingly, the PNU-120596 agonist co-application data revealed that for wild-type ?7 nAChR, the 3-furan desensitized state was relatively stabilized compared with that of 2-furan, a reversal of the relationship observed with respect to the barrier for entry into the desensitized state. These data highlight the importance of hydrogen bonding on the receptor-ligand state, and suggest that it may be possible to fine-tune features of agonists that mediate state selection in the nAChR.
Related JoVE Video
Hippocampal theta-driving cells revealed by Granger causality.
Hippocampus
Show Abstract
Hide Abstract
The two-dipole model of theta generation in hippocampal CA1 suggests that the inhibitory perisomatic theta dipole is generated by local GABAergic interneurons. Various CA1 interneurons fire preferentially at different theta phases, raising the question of how these theta-locked interneurons contribute to the generation of theta oscillations. We here recorded interneurons in the hippocampal CA1 area of freely behaving mice, and identified a unique subset of theta-locked interneurons by using the Granger causality approach. These cells fired in an extremely reliable theta-burst pattern at high firing rates (?90 Hz) during exploration and always locked to ascending phases of the theta waves. Among theta-locked interneurons we recorded, only these cells generated strong Granger causal influences on local field potential (LFP) signals within the theta band (4-12 Hz), and the influences were persistent across behavioral states. Our results suggest that this unique type of theta-locked interneurons serve as the local inhibitory theta dipole control cells in shaping hippocampal theta oscillations.
Related JoVE Video

What is Visualize?

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

How does it work?

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

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

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