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.
Asymmetric Hetero-Diels-Alder Reaction of Diazenes Catalyzed by Chiral Silver Phosphate: Water Participates in the Catalysis and Stereocontrol.
Org. Lett.
PUBLISHED: 11-20-2014
Show Abstract
Hide Abstract
The chiral silver phosphate was confirmed to efficiently catalyze a highly regio- and enantioselective hetero-Diels-Alder reaction of diazenes to furnish piperazine derivatives in high yields and excellent ee values. DFT calculations revealed that the water molecule participates in the catalysis by coordination to silver phosphate and also found that the hydroxy group of 1-hydroxy-2,3-hexadiene not only formed a hydrogen bond with the oxygen of phosphate but also coordinated to the Ag(I) to simultaneously stabilize the transition states and control the regioselectivity.
Related JoVE Video
Radiofrequency catheter ablation at the non-coronary cusp for the treatment of para-hisian accessory pathways.
Europace
PUBLISHED: 10-31-2014
Show Abstract
Hide Abstract
Radiofrequency catheter ablation (RFCA) is well established as a definitive therapy of accessory pathways (APs). Successful RFCA of anteroseptal APs at the non-coronary cusp (NCC) have been reported in several case reports. We aimed to evaluate the prevalence, safety, efficacy, and long-term outcome of RFCA at the NCC for the treatment of para-hisian APs.
Related JoVE Video
Microstructure Tailoring of the Nickel Oxide-Yttria-Stabilized Zirconia Hollow Fibers toward High-Performance Microtubular Solid Oxide Fuel Cells.
ACS Appl Mater Interfaces
PUBLISHED: 10-29-2014
Show Abstract
Hide Abstract
NiO-yttria-stabilized zirconia (YSZ) hollow fiber anode support with different microstructures was prepared using a phase-inversion method. The effect of the solid loading of the phase-inversion suspensions on the microstructure development of the NiO-YSZ anode support was investigated. Solid loading in the suspension was found to have an important influence on the microstructure of the NiO-YSZ anode support and viscosity-related viscous fingering mechanism can be adopted to explain the pore formation mechanism of the as-prepared hollow fibers. NiO-YSZ anode-supported microtubular solid oxide fuel cells (SOFCs) with different anode microstructures were fabricated and tested, and the correlation between the anode support microstructures, porosity, gas permeability, electrical conductivity, and the cell electrochemical performance was discussed. Microtubular SOFCs with a cell configuration of Ni-YSZ/YSZ/YSZ-LSM (LSM = (La0.8Sr0.2)0.95MnO3-x) and optimized anode microstructure show cell output power density of 833.9 mW cm(-2) at 750 °C using humidified H2 as fuel and ambient air as oxidant.
Related JoVE Video
[Cloning, identification and preliminary functional analysis of odorant receptor 7 gene of Aedes albopictus].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 10-28-2014
Show Abstract
Hide Abstract
To clone and identify olfactory receptor odorant receptor 7 (OR7) gene of Aedes albopictus and analyze its expression profile and calcium regulation function.
Related JoVE Video
Preoperative serum alkaline phosphatase: a predictive factor for early hypocalcaemia following parathyroidectomy of primary hyperparathyroidism.
Chin. Med. J.
PUBLISHED: 10-01-2014
Show Abstract
Hide Abstract
Postoperative hypocalcemia is one of the most common complications following parathyroidectomy for primary hyperparathyroidism (PHPT). The aim of this study was to analyze the predictive value of biochemical parameters as indicators for episodes of hypocalcemia in patients undergoing parathyroidectomy for PHPT.
Related JoVE Video
Discrete potentials guided radiofrequency ablation for idiopathic outflow tract ventricular arrhythmias.
Europace
PUBLISHED: 09-01-2014
Show Abstract
Hide Abstract
Discrete potentials (DPs) have been recorded and targeted as the site of ablation of the outflow tract arrhythmias. The aim of the present study was to investigate the significance of DPs with respect to mapping and ablation for idiopathic outflow tract premature ventricular contractions (PVCs) or ventricular tachycardias (VTs).
Related JoVE Video
HER2/neu over-expression predicts poor outcome in early gastric cancer without lymph node metastasis.
Clin Res Hepatol Gastroenterol
PUBLISHED: 08-28-2014
Show Abstract
Hide Abstract
Human epidermal growth factor receptor 2 (HER2/neu) is involved in the pathogenesis of several types of cancer, including gastric cancer. However, there remains a paucity of data regarding the prognostic relevance of HER2/neu in early gastric cancer without lymph node metastasis (pN0 EGC). The aim of our study was to analyze whether the over-expression of HER2/neu significantly predicts poor outcomes of pN0 EGC.
Related JoVE Video
Three-dimensional reconstruction method for measuring the knee valgus angle of the femur in northern Chinese adults.
J Zhejiang Univ Sci B
PUBLISHED: 08-06-2014
Show Abstract
Hide Abstract
The purpose of this study was to establish a method for measuring the knee valgus angle from the anatomical and mechanical axes on three-dimensional reconstruction imaging models, and to use this method for estimating an average knee valgus angle value for northern Chinese adults. Computed tomographic angiography data in DICOM format for 128 normal femurs from 64 adult subjects were chosen for analysis. After the femur images were subjected to three-dimensional reconstruction, the deepest point in the intercondylar notch (point A), the midpoint of the medullary cavity 20 cm above the knee-joint line (point B), and the landmark of the femoral head rotation center (point C) were identified on each three-dimensional model. The knee valgus angle was defined as the angle enclosed by the distal femoral anatomical axis (line AB) and the femoral mechanical axis (line AC). The average (mean±SD) of knee valgus angle for the 128 femurs was 6.20°±1.20° (range, 3.05° to 10.64°). Significant positive correlations were found between the knee valgus angles of the right and left sides and between the knee valgus angle and age. During total knee arthroplasty, choosing a valgus cut angle of approximately 6° may achieve a good result in reestablishing the natural mechanical alignment of the lower extremity for patients of northern Chinese ethnicity. Larger valgus cut angles should be chosen for older patients.
Related JoVE Video
Deep sequencing of the scallop Chlamys farreri transcriptome response to tetrabromobisphenol A (TBBPA) stress.
Mar Genomics
PUBLISHED: 08-04-2014
Show Abstract
Hide Abstract
Tetrabromobisphenol-A (TBBPA) is currently the most widely used brominated flame retardant (BFR) and has been proven to have a very high toxicity to aquatic organisms including bivalves. However, molecular responses to TBBPA in bivalve remain largely unknown. Novel high-throughput deep sequencing technology has been a powerful tool for looking at molecular responses to toxicological stressors in organisms. Using Illumina's digital gene expression (DGE) system, we investigated TBBPA-induced transcriptome response in the digestive gland tissue of scallop Chlamys farreri. In total, 173 and 266 genes were identified as significantly up- or down-regulated, respectively. Functional analysis based on gene ontology (GO) classification system and Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that TBBPA significantly altered the expression of genes involved in stress response, detoxification, antioxidation, and innate immunity which were extensively discussed. In particular, evidence for the endocrine disrupting effect of TBBPA on bivalve was first obtained in this study. Quantitative real-time PCR was performed to ascertain the mRNA expression of several genes identified by the DGE analysis. The results of this study may serve as a basis for future research on molecular mechanism of toxic effects of TBBPA on marine bivalves.
Related JoVE Video
The role of interleukin-28b gene polymorphisms in chinese patients with chronic hepatitis C treated with pegylated interferon and ribavirin.
Hepat Mon
PUBLISHED: 08-01-2014
Show Abstract
Hide Abstract
Interleukin-28B (IL28B) single nucleotide polymorphism (SNP) rs8099917 has been described to be associated with response to treatment with pegylated interferon and ribavirin (PEG-IFN/RBV) in patients with chronic hepatitis C from the North America, Europe, Asia countries like Japan and Taiwan. Whether this holds true for Chinese patients remains unknown.
Related JoVE Video
Diabetes mellitus and atrial remodeling: mechanisms and potential upstream therapies.
Cardiovasc Ther
PUBLISHED: 07-29-2014
Show Abstract
Hide Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, and its prevalence has increasing substantially over the last decades. Recent data suggest that there is an increased risk of AF among the patients with diabetes mellitus (DM). However, the potential molecular mechanisms regarding DM-related AF and diabetic atrial remodeling are not fully understood. In this comprehensive review, we would like to summarize the potential relationship between diabetes and atrial remodeling, including structural, electrical, and autonomic remodeling. Also, some upstream therapies, such as thiazolidinediones, probucol, ACEI/ARBs, may play an important role in the prevention and treatment of AF. Therefore, large prospective randomized, controlled trials and further experimental studies should be challengingly continued.
Related JoVE Video
Downregulation of Ras GTPase?activating protein 1 is associated with poor survival of breast invasive ductal carcinoma patients.
Oncol. Rep.
PUBLISHED: 07-14-2014
Show Abstract
Hide Abstract
Ras GTPase?activating protein 1 (RASA1) functions to inactivate Ras?GTPase and inhibit the mitogenic signal. Reduction or loss of RASA1 expression occurs during human cancer development and progression. This study investigated RASA1 expression in normal and breast cancer tissue specimens to determine the association with prognosis of breast cancer patients. Two sets of patient samples (45 fresh tissues and 373 paraffin?embedded tissues) were analyzed for RASA1 expression using RT?qPCR and immunohisto-chemistry. The results showed that the expression of RASA1 mRNA was lower in breast cancer tissues than in the corresponding normal tissues (P<0.001). Additionally, RASA1 expression was reduced in 60.6% (226/373) of breast cancer tissues. The reduced RASA1 expression was significantly associated with tumor lymph node metastasis (P=0.002), advanced TNM stages (P=0.017), estrogen receptor (ER) expression (P=0.002), Ki?67 (P=0.009), higher histological grade (P<0.001), and triple?negative breast cancer (P=0.041). Moreover, the reduced RASA1 expression was associated with shorter disease?free survival (P=0.036) and overall survival (P<0.001) of breast cancer patients. RASA1 expression, together with tumor lymph?node metastasis, TNM stage, Her?2 expression, and triple?negative breast cancer were independent factors in predicting survival of breast cancer patients. In conclusion, RASA1 expression is frequently reduced in breast cancer tissues, and the reduced RASA1 expression is associated with breast cancer progression and poor survival and disease?free survival of patients.
Related JoVE Video
Immunosuppressive treatment for myocarditis: a meta-analysis of randomized controlled trials.
J Cardiovasc Med (Hagerstown)
PUBLISHED: 07-09-2014
Show Abstract
Hide Abstract
Immunosuppressive treatment for myocarditis is controversial. Several small-scale randomized controlled trials (RCTs) reported inconsistent outcomes for patients with myocarditis.
Related JoVE Video
Thermodynamic mechanism for the evasion of antibody neutralization in flaviviruses.
J. Am. Chem. Soc.
PUBLISHED: 07-08-2014
Show Abstract
Hide Abstract
Mutations in the epitopes of antigenic proteins can confer viral resistance to antibody-mediated neutralization. However, the fundamental properties that characterize epitope residues and how mutations affect antibody binding to alter virus susceptibility to neutralization remain largely unknown. To address these questions, we used an ensemble-based algorithm to characterize the effects of mutations on the thermodynamics of protein conformational fluctuations. We applied this method to the envelope protein domain III (ED3) of two medically important flaviviruses: West Nile and dengue 2. We determined an intimate relationship between the susceptibility of a residue to thermodynamic perturbations and epitope location. This relationship allows the successful identification of the primary epitopes in each ED3, despite their high sequence and structural similarity. Mutations that allow the ED3 to evade detection by the antibody either increase or decrease conformational fluctuations of the epitopes through local effects or long-range interactions. Spatially distant interactions originate in the redistribution of conformations of the ED3 ensembles, not through a mechanically connected array of contiguous amino acids. These results reconcile previous observations of evasion of neutralization by mutations at a distance from the epitopes. Finally, we established a quantitative correlation between subtle changes in the conformational fluctuations of the epitope and large defects in antibody binding affinity. This correlation suggests that mutations that allow viral growth, while reducing neutralization, do not generate significant structural changes and underscores the importance of protein fluctuations and long-range interactions in the mechanism of antibody-mediated neutralization resistance.
Related JoVE Video
Probucol Prevents Atrial Remodeling by Inhibiting Oxidative Stress and TNF-?/NF-?B/TGF-? Signal Transduction Pathway in Alloxan-induced Diabetic Rabbits.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 06-29-2014
Show Abstract
Hide Abstract
Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). However, the underlying mechanisms for the increased propensity for AF in the setting of DM and the potential effects of probucol on atrial remodeling remain unclear.
Related JoVE Video
Deep sequencing-based transcriptome profiling analysis of Chlamys farreri exposed to benzo[a]pyrene.
Gene
PUBLISHED: 06-05-2014
Show Abstract
Hide Abstract
Whole-genome transcriptome measurements are pivotal for characterizing molecular mechanisms of chemicals and predicting toxic classes, such as genotoxicity and carcinogenicity, from in vitro and in vivo assays. We analyzed the dynamic defense transcriptome responsive to Chlamys farreri upon exposure to benzo[a]pyrene (BaP) using a digital gene expression (DGE) approach. Following exposure, 251 and 177 genes were up-regulated, and 142 and 300 genes were down-regulated at 3 days post-exposure and 10 days post-exposure, respectively. The differentially expressed genes were related to toxicological response, oxidative stress and the metabolism of proteins and fats. Of these genes, most genes up-regulated at the early stage of exposure tended to be constantly down-regulated at the later stage whereas the landscape of the up- or down-regulated genes differed significantly at the two time points investigated. Functional enrichment analyses show that RNA-seq yields more insight into the biological mechanisms related to the toxic effects caused by BaP, i.e., two to fivefold more affected pathways and biological processes. Besides, we observed a change in the expression of ten genes which are important and differentially-expressed detoxification-related genes, and this was subsequently confirmed via quantitative real-time PCR. Our results provide evidence that RNA-seq is a powerful tool for toxicology and is capable of generating novel and valuable information at the transcriptome level for characterizing deleterious effects caused by BaP.
Related JoVE Video
Prognostic effect of p53 expression in patients with completely resected colorectal cancer.
Tumour Biol.
PUBLISHED: 05-25-2014
Show Abstract
Hide Abstract
The p53 protein is closely involved in the carcinogenesis of many kinds of cancers. Though the prognostic role of p53 expression for the survival of colorectal cancer (CRC) patients has been preliminarily identified, the prognostic effect of p53 expression in patients with completely resected CRC is still unclear. Therefore, a retrospective cohort study was performed to assess the prognostic role of p53 expression for overall survival in patients with completely resected CRC. A total of 153 patients (mean age 50.9 years) with completely resected CRC was finally included in the retrospective cohort study. Kaplan-Meier product-limit methods and log-rank test were used to estimate overall survival distribution and test the difference. In addition, multivariable analysis by Cox regression model was also used to test the prognostic role of p53 expression on overall survival by adjusting for other confounding factors. Of those 153 CRC patients, 62 (40.5 %) were positive for p53 protein expression in the tumor tissues. The log-rank test showed that there was an obvious difference in the overall survival between the p53-positive group and the p53-negative group (P?
Related JoVE Video
Requirement of B7-H1 in mesenchymal stem cells for immune tolerance to cardiac allografts in combination therapy with rapamycin.
Transpl. Immunol.
PUBLISHED: 05-20-2014
Show Abstract
Hide Abstract
The potential of mesenchymal stem cells (MSCs) for immunosuppression has been tested in transplantation, but its mechanisms are not fully understood. This study investigated the role of MSC-expressing B7-H1 in the induction of immune tolerance to cardiac allografts by the combination therapy of MSCs and rapamycin (RAPA).
Related JoVE Video
[A comparative analysis of the passive electric probe detection and spectrum diagnosis of laser-induced plasma].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 05-15-2014
Show Abstract
Hide Abstract
An approach to detecting laser-induced plasma using passive probe was brought up. The plasma of laser welding was studied by using a synchronous electric and spectral information acquisition system, the laser-induced plasma was detected by a passive electric probe and fiber spectrometer, the electrical signal was analyzed on the basis of the theory of plasma sheath, and the temperature of laser-induced plasma was calculated by using the method of relative spectral intensity. The analysis results from electrical signal and spectral one were compared. Calculation results of three kinds of surface circumstances, which were respectively coated by KF, TiO2 and without coating, were compared. The factors affecting the detection accuracy were studied. The results indicated that the results calculated by passive probe matched that by spectral signal basically, and the accuracy was affected by ions mass of the plasma. The designed passive electric probe can be used to reflect the continuous fluctuation of electron temperature of the generated plasma, and monitor the laser-induced plasma.
Related JoVE Video
Rosiglitazone attenuates atrial structural remodeling and atrial fibrillation promotion in alloxan-induced diabetic rabbits.
Cardiovasc Ther
PUBLISHED: 05-13-2014
Show Abstract
Hide Abstract
The pleiotropic effects of glitazones may favorably affect atrial remodeling. We sought to investigate the effects of peroxisome proliferator-activated receptor-? (PPAR-?) activator rosiglitazone on atrial structural remodeling and atrial fibrillation (AF) promotion in alloxan-induced diabetic rabbits.
Related JoVE Video
Oxidative stress and genotoxicity of the ionic liquid 1-octyl-3-methylimidazolium bromide in zebrafish (Danio rerio).
Arch. Environ. Contam. Toxicol.
PUBLISHED: 05-09-2014
Show Abstract
Hide Abstract
Ionic liquids (ILs) have a great reputation due to their negligible volatility, designability, good stability, and ability to be recycled. They are considered to be "green" solvents and have great promise in many fields. In recent years, the toxicities of ILs have garnered increasing attention as reported by a number of studies. However, previous studies have primarily focused on their lethal toxicities, and data were limited on their toxic effects at nonlethal doses. We performed a study on the toxic effects of 1-octyl-3-methylimidazolium bromide ([Omim]Br) on zebrafish. During a 28-day period, male and female zebrafish were separately exposed to sequential concentrations (0, 5, 10, 20, and 40 mg/L) of [Omim]Br. Fishes were sampled after 7, 14, 21, and 28 days of exposure, and reactive oxygen species (ROS) levels, activities of antioxidant enzymes (superoxide dismutase and catalase), lipid peroxidation (LPO), and DNA damage in fish livers were measured. ROS, LPO, and DNA damage were all induced by the ionic liquid, and antioxidant enzyme activities increased at the beginning and then decreased. These phenomena demonstrate that [Omim]Br can induce oxidative stress and DNA damage in zebrafish.
Related JoVE Video
Clinical outcome of ileal pouch-anal anastomosis for chronic ulcerative colitis in China.
Chin. Med. J.
PUBLISHED: 04-26-2014
Show Abstract
Hide Abstract
The incidence of chronic ulcerative colitis (CUC) in China is remarkably increasing, while little information on surgical treatment has been reported. This study aimed to completely describe and analyze the clinical outcome of restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for CUC in China.
Related JoVE Video
Adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis.
Scand. J. Gastroenterol.
PUBLISHED: 04-14-2014
Show Abstract
Hide Abstract
The aim of this article is to review up-to-date clinical data published in the literature in regard to adjuvant chemotherapy in patients with gastric cancer after radical surgical resection.
Related JoVE Video
[Research on the suppressive effect on transplantation rejection by indoleamine 2, 3-dioxygenase].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 04-05-2014
Show Abstract
Hide Abstract
To study the suppressive effect of indoleamine 2, 3-dioxygenase on transplantation rejection in mice heterotopic cardiac transplantation.
Related JoVE Video
Structural insights into RNA encapsidation and helical assembly of the Toscana virus nucleoprotein.
Nucleic Acids Res.
PUBLISHED: 03-31-2014
Show Abstract
Hide Abstract
Toscana virus is an emerging bunyavirus in Mediterranean Europe where it accounts for 80% of pediatric meningitis cases during the summer. The negative-strand ribonucleic acid (RNA) genome of the virus is wrapped around the virally encoded nucleoprotein N to form the ribonucleoprotein complex (RNP). We determined crystal structures of hexameric N alone (apo) and in complex with a nonameric single-stranded RNA. RNA is sequestered in a sequence-independent fashion in a deep groove inside the hexamer. At the junction between two adjacent copies of Ns, RNA binding induced an inter-subunit rotation, which opened the RNA-binding tunnel and created a new assembly interface at the outside of the hexamer. Based on these findings, we suggest a structural model for how binding of RNA to N promotes the formation of helical RNPs, which are a characteristic hallmark of many negative-strand RNA viruses.
Related JoVE Video
Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL.
Mol. Cell
PUBLISHED: 03-15-2014
Show Abstract
Hide Abstract
The Hippo pathway, evolutionarily conserved from flies to mammals, promotes cell death and inhibits cell proliferation to regulate organ size. The core component of this cascade, Mst1 in mammalian cells, is sufficient to promote apoptosis. However, the mechanisms underlying both its activation and its ability to elicit cell death remain largely undefined. We here identify a signaling cassette in cardiac myocytes consisting of K-Ras, the scaffold RASSF1A, and Mst1 that is localized to mitochondria and promotes Mst1 activation in response to oxidative stress. Activated Mst1 phosphorylates Bcl-xL at Ser14, which resides in the BH4 domain, thereby antagonizing Bcl-xL-Bax binding. This, in turn, causes activation of Bax and subsequent mitochondria-mediated apoptotic death. Our findings demonstrate mitochondrial localization of Hippo signaling and identify Bcl-xL as a target that is directly modified to promote apoptosis.
Related JoVE Video
Drosophila pheromone-sensing neurons expressing the ppk25 ion channel subunit stimulate male courtship and female receptivity.
PLoS Genet.
PUBLISHED: 03-01-2014
Show Abstract
Hide Abstract
As in many species, gustatory pheromones regulate the mating behavior of Drosophila. Recently, several ppk genes, encoding ion channel subunits of the DEG/ENaC family, have been implicated in this process, leading to the identification of gustatory neurons that detect specific pheromones. In a subset of taste hairs on the legs of Drosophila, there are two ppk23-expressing, pheromone-sensing neurons with complementary response profiles; one neuron detects female pheromones that stimulate male courtship, the other detects male pheromones that inhibit male-male courtship. In contrast to ppk23, ppk25, is only expressed in a single gustatory neuron per taste hair, and males with impaired ppk25 function court females at reduced rates but do not display abnormal courtship of other males. These findings raised the possibility that ppk25 expression defines a subset of pheromone-sensing neurons. Here we show that ppk25 is expressed and functions in neurons that detect female-specific pheromones and mediates their stimulatory effect on male courtship. Furthermore, the role of ppk25 and ppk25-expressing neurons is not restricted to responses to female-specific pheromones. ppk25 is also required in the same subset of neurons for stimulation of male courtship by young males, males of the Tai2 strain, and by synthetic 7-pentacosene (7-P), a hydrocarbon normally found at low levels in both males and females. Finally, we unexpectedly find that, in females, ppk25 and ppk25-expressing cells regulate receptivity to mating. In the absence of the third antennal segment, which has both olfactory and auditory functions, mutations in ppk25 or silencing of ppk25-expressing neurons block female receptivity to males. Together these results indicate that ppk25 identifies a functionally specialized subset of pheromone-sensing neurons. While ppk25 neurons are required for the responses to multiple pheromones, in both males and females these neurons are specifically involved in stimulating courtship and mating.
Related JoVE Video
Phase, microstructure and hydrogen storage properties of Mg-Ni materials synthesized from metal nanoparticles.
Nanotechnology
PUBLISHED: 02-28-2014
Show Abstract
Hide Abstract
After Mg and Ni nanoparticles were fabricated by hydrogen plasma metal reaction, Mg-rich MgxNi????x(75 < x < 90) materials were synthesized from these metal nanoparticles to study the synergistic effects for hydrogen storage in these samples to show both good kinetics and high capacity. These MgxNi????x materials may absorb hydrogen with a capacity of around 3.3-5.1 wt% in 1 min at 573 K. The Mg??Ni?? sample shows a hydrogen capacity of 6.1 wt%. The significant kinetic enhancement is thought to be due to the unique nanostructure from the special synthesis route, the catalytic effect of the Mg?Ni nano phase, and the synergistic effects between the Mg?Ni and Mg phases in the materials. An interesting phenomenon which has never been reported before was observed during pressure composition isotherm (PCT) measurements. One steep step in the absorption process and two obviously separated steps in the desorption process during PCT measurements of Mg??Ni?? and Mg??Ni?? samples were observed and a possible reason from the kinetic performance of the Mg?Ni and Mg phases in absorption and desorption processes was explained. These MgxNi????x materials synthesized from Mg and Ni nanoparticles show high capacity and good kinetics, which makes these materials very promising candidates for thermal storage or energy storage and utilization for renewable power.
Related JoVE Video
A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief.
Cell
PUBLISHED: 02-25-2014
Show Abstract
Hide Abstract
Voltage-gated sodium (NaV) channels control the upstroke of the action potentials in excitable cells. Multiple studies have shown distinct roles of NaV channel subtypes in human physiology and diseases, but subtype-specific therapeutics are lacking and the current efforts have been limited to small molecules. Here, we present a monoclonal antibody that targets the voltage-sensor paddle of NaV1.7, the subtype critical for pain sensation. This antibody not only inhibits NaV1.7 with high selectivity, but also effectively suppresses inflammatory and neuropathic pain in mice. Interestingly, the antibody inhibits acute and chronic itch despite well-documented differences in pain and itch modulation. Using this antibody, we discovered that NaV1.7 plays a key role in spinal cord nociceptive and pruriceptive synaptic transmission. Our studies reveal that NaV1.7 is a target for itch management, and the antibody has therapeutic potential for suppressing pain and itch. Our antibody strategy may have broad applications for voltage-gated cation channels.
Related JoVE Video
The Effects of Needling Fenglong (ST40) and Neiguan (PC6) on IL-17 of ApoE-Gene-Knockout Mice's Liver.
Evid Based Complement Alternat Med
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
The aim of the present paper was to observe the effects of needling ST40 and PC6 on IL-17 of ApoE(-/-) mice with fatty liver. Forty male ApoE(-/-) mice were randomized into Needling-Acupoint Group, Simvastatin Intragastric Administration Group, Needling Nonacupoint Group, and Model Group. Each was fed with high fat diet for 8 weeks since 16 weeks of age; after 8 weeks of intervention, mice were sacrificed and tested for various examinations. Result showed that the body weight, TC, and serum IL-17 in Needling-Acupoint Group decreased. Compared with Model Group, the immunohistochemical expressions of IL-17 in liver tissue were significantly decreased among the other three groups. In conclusion, acupuncture was able to lower the expression of IL-17 level both in serum and liver tissue in ApoE(-/-) mice, which is helpful to reduce the inflammation and defers the progress from fatty liver to cirrhosis.
Related JoVE Video
The cytotoxic and genotoxic effects of metalaxy-M on earthworms (Eisenia fetida).
Environ. Toxicol. Chem.
PUBLISHED: 02-17-2014
Show Abstract
Hide Abstract
As the main optical isomer of metalaxyl, metalaxyl-M has been widely used worldwide in recent years because of its notable effect on the prevention and control of crop diseases. Together with the toxicity and degradation of metalaxyl-M, the chemical has attracted the attention of researchers. The present study examined the toxic effects of metalaxyl-M on earthworms at 0?mg?kg(-1) , 0.1?mg?kg(-1) , 1?mg?kg(-1) , and 3?mg?kg(-1) on days 7, 14, 21 and 28 after exposure. The results showed that metalaxyl-M could cause an obvious increase in the production of reactive oxygen species (ROS) when the concentration was higher than 0.1?mg?kg(-1) , which led to lipid peroxidation in earthworms. Metalaxyl-M can induce DNA damage in earthworms, and the level of DNA damage markedly increased with increasing the concentration of metalaxyl-M. Metalaxyl-M also has a serious influence on the activities of antioxidant enzymes, which results in irreversible oxidative damage in cells. The changes of these indicators all indicated that metalaxyl-M may cause cytotoxic and genotoxic effects on earthworms.
Related JoVE Video
Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-? secretion.
J. Clin. Invest.
PUBLISHED: 02-17-2014
Show Abstract
Hide Abstract
Increasing evidence indicates that the pathogenesis of neuropathic pain is mediated through spinal cord microglia activation. The intracellular protease caspase-6 (CASP6) is known to regulate neuronal apoptosis and axonal degeneration; however, the contribution of microglia and CASP6 in modulating synaptic transmission and pain is unclear. Here, we found that CASP6 is expressed specifically in C-fiber axonal terminals in the superficial spinal cord dorsal horn. Animals exposed to intraplantar formalin or bradykinin injection exhibited CASP6 activation in the dorsal horn. Casp6-null mice had normal baseline pain, but impaired inflammatory pain responses. Furthermore, formalin-induced second-phase pain was suppressed by spinal injection of CASP6 inhibitor or CASP6-neutralizing antibody, as well as perisciatic nerve injection of CASP6 siRNA. Recombinant CASP6 (rCASP6) induced marked TNF-? release in microglial cultures, and most microglia within the spinal cord expressed Tnfa. Spinal injection of rCASP6 elicited TNF-? production and microglia-dependent pain hypersensitivity. Evaluation of excitatory postsynaptic currents (EPSCs) revealed that rCASP6 rapidly increased synaptic transmission in spinal cord slices via TNF-? release. Interestingly, the microglial inhibitor minocycline suppressed rCASP6 but not TNF-?-induced synaptic potentiation. Finally, rCASP6-activated microglial culture medium increased EPSCs in spinal cord slices via TNF-?. Together, these data suggest that CASP6 released from axonal terminals regulates microglial TNF-? secretion, synaptic plasticity, and inflammatory pain.
Related JoVE Video
Relationship between two arrhythmias: sinus node dysfunction and atrial fibrillation.
Arch. Med. Res.
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
We reviewed recent advancements in the relationship between sinus node dysfunction (SND) and atrial fibrillation (AF) and propose some underlying mechanisms in regard to ion and molecular aspects. The amount of clinical and animal experiments have proven the structural and electrophysiological remodeling of sinoatrial node (SAN) and atrium may be related significantly between SND and AF. Atrial remodeling was often related to RAS activation. RAS inhibitors and statin, which resist in atrial fibrosis, may be novel strategies to prevent or treat both SND and AF. Besides, funny current (If) and Ca(2+) clock mainly contributing to the SAN automaticity may be another link between SND and AF. Gap junctions such as Cx40, Cx43 and Cx45 were proven to participate in both automaticity and conductivity of electrical impulses in SAN and atrial tissue, which was accepted as another link between SND and AF. Common genetic mutations such as the emerin gene, SCN5A gene and HCN4 gene mutation were also the mechanism for the correlation between SND and AF.
Related JoVE Video
Improved method for planning intramedullary guiding rod entry point in total knee arthroplasty.
Arch Orthop Trauma Surg
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
To study the accuracy of using the deepest point of the intercondylar notch (DPIN) as a reference point for femoral intramedullary (IM) guiding rod entrance in total knee arthroplasty (TKA) with 3-D reconstruction in Chinese subjects.
Related JoVE Video
A redox-dependent mechanism for regulation of AMPK activation by Thioredoxin1 during energy starvation.
Cell Metab.
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
5'-AMP-activated protein kinase (AMPK) is a key regulator of metabolism and survival during energy stress. Dysregulation of AMPK is strongly associated with oxidative-stress-related disease. However, whether and how AMPK is regulated by intracellular redox status remains unknown. Here we show that the activity of AMPK is negatively regulated by oxidation of Cys130 and Cys174 in its ? subunit, which interferes with the interaction between AMPK and AMPK kinases (AMPKK). Reduction of Cys130/Cys174 is essential for activation of AMPK during energy starvation. Thioredoxin1 (Trx1), an important reducing enzyme that cleaves disulfides in proteins, prevents AMPK oxidation, serving as an essential cofactor for AMPK activation. High-fat diet consumption downregulates Trx1 and induces AMPK oxidation, which enhances cardiomyocyte death during myocardial ischemia. Thus, Trx1 modulates activation of the cardioprotective AMPK pathway during ischemia, functionally linking oxidative stress and metabolism in the heart.
Related JoVE Video
Protective effects of aliskiren on atrial ionic remodeling in a canine model of rapid atrial pacing.
Cardiovasc Drugs Ther
PUBLISHED: 02-04-2014
Show Abstract
Hide Abstract
Aliskiren inhibits the activation of the renin-angiotensin system. Here, we investigated the effects of aliskiren on chronic atrial iron remodeling in the experimental canine model of rapid atrial pacing.
Related JoVE Video
B-cell epitopes in GroEL of Francisella tularensis.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The chaperonin protein GroEL, also known as heat shock protein 60 (Hsp60), is a prominent antigen in the human and mouse antibody response to the facultative intracellular bacterium Francisella tularensis (Ft), the causative agent of tularemia. In addition to its presumed cytoplasmic location, FtGroEL has been reported to be a potential component of the bacterial surface and to be released from the bacteria. In the current study, 13 IgG2a and one IgG3 mouse monoclonal antibodies (mAbs) specific for FtGroEL were classified into eleven unique groups based on shared VH-VL germline genes, and seven crossblocking profiles revealing at least three non-overlapping epitope areas in competition ELISA. In a mouse model of respiratory tularemia with the highly pathogenic Ft type A strain SchuS4, the Ab64 and N200 IgG2a mAbs, which block each other's binding to and are sensitive to the same two point mutations in FtGroEL, reduced bacterial burden indicating that they target protective GroEL B-cell epitopes. The Ab64 and N200 epitopes, as well as those of three other mAbs with different crossblocking profiles, Ab53, N3, and N30, were mapped by hydrogen/deuterium exchange-mass spectrometry (DXMS) and visualized on a homology model of FtGroEL. This model was further supported by its experimentally-validated computational docking to the X-ray crystal structures of Ab64 and Ab53 Fabs. The structural analysis and DXMS profiles of the Ab64 and N200 mAbs suggest that their protective effects may be due to induction or stabilization of a conformational change in FtGroEL.
Related JoVE Video
High levels of BCOX1 expression are associated with poor prognosis in patients with invasive ductal carcinomas of the breast.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
This study was to examine the breast cancer-overexpressed gene 1 (BCOX1) expression in invasive ductal carcinomas (IDC) of the breast and its value in the prognosis of the disease. The levels of BCOX1 expression in 491 paired IDC and surrounding non-tumor breast tissues as well as 40 paired fresh specimens were evaluated by tissue microarray, immunohistochemistry and quantitative RT-PCR. The potential associations of high BCOX1 expression with clinicopathological variables and the overall survival of these patients were analyzed. The relative levels of BCOX1 mRNA transcripts in the IDC breast tissues were significantly higher than that in the corresponding non-tumor tissues (P = 0.005). The anti-BCOX1 was predominantly stained in the cytoplasm of breast tissue cells and the levels of BCOX1 expression in the majority of breast cancer tissues were obviously higher than that in the corresponding non-tumor breast tissues. High levels of BCOX1 expression were found in 59.5% (292/491) of breast cancer tissues. The high BCOX1 expression was significantly associated with high histological grade (P = 0.037), positive expression of human epidermal growth factor receptor 2 (HER2, P = 0.031) and triple negative breast cancer (P = 0.027). The high BCOX1 expression in breast cancers was significantly associated with a shorter overall survival of these patients (P = 0.023), particularly in patients with triple negative breast cancer (P = 0.005). Therefore, the high BCOX1 expression may serve as a novel marker of poor prognosis and a potential therapeutic target for patients with IDC of the breast.
Related JoVE Video
Efficient reprogramming of naïve-like induced pluripotent stem cells from porcine adipose-derived stem cells with a feeder-independent and serum-free system.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed by ectopic expression of transcription factors or small molecule treatment, which resemble embryonic stem cells (ESCs). They hold great promise for improving the generation of genetically modified large animals. However, few porcine iPSCs (piPSCs) lines obtained currently can support development of cloned embryos. Here, we generated iPSCs from porcine adipose-derived stem cells (pADSCs), using drug-inducible expression of defined human factors (Oct4, Sox2, c-Myc and Klf4). Reprogramming of iPSCs from pADSCs was more efficient than from fibroblasts, regardless of using feeder-independent or feeder-dependent manners. By addition of Lif-2i medium containing mouse Lif, CHIR99021 and PD0325901 (Lif-2i), naïve-like piPSCs were obtained under feeder-independent and serum-free conditions. These successfully reprogrammed piPSCs were characterized by short cell cycle intervals, alkaline phosphatase (AP) staining, expression of Oct4, Sox2, Nanog, SSEA3 and SSEA4, and normal karyotypes. The resemblance of piPSCs to naïve ESCs was confirmed by their packed dome morphology, growth after single-cell dissociation, Lif-dependency, up-regulation of Stella and Eras, low expression levels of TRA-1-60, TRA-1-81 and MHC I and activation of both X chromosomes. Full reprogramming of naïve-like piPSCs was evaluated by the significant up-regulation of Lin28, Esrrb, Utf1 and Dppa5, differentiating into cell types of all three germ layers in vitro and in vivo. Furthermore, nuclear transfer embryos from naïve-like piPSCs could develop to blastocysts with improved quality. Thus, we provided an efficient protocol for generating naïve-like piPSCs from pADSCs in a feeder-independent and serum-free system with controlled regulation of exogenous genes, which may facilitate optimization of culture media and the production of transgenic pigs.
Related JoVE Video
[Efficacy of postoperative simple chemotherapy and concurrent chemoradiotherapy in FIGO stage IB2-IIB cervical cancer].
Beijing Da Xue Xue Bao
PUBLISHED: 12-18-2013
Show Abstract
Hide Abstract
To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer.
Related JoVE Video
Study of circulating antibodies against CD25 and FOXP3 in breast cancer.
Tumour Biol.
PUBLISHED: 11-11-2013
Show Abstract
Hide Abstract
Our recent work suggests that circulating levels of anti-CD25 and anti-FOXP3 antibodies were significantly increased in patients with either lung cancer or esophageal cancer. To confirm if these two autoantibodies are specific for certain types of malignant tumors, the present work was thus undertaken to examine an alteration of anti-CD25 and anti-FOXP3 IgG levels in breast cancer. A total of 152 patients with breast cancer and 112 control subjects were recruited in this study. The levels of circulating anti-CD25 and anti-FOXP3 IgG antibodies were tested using an in-house enzyme-linked immunosorbent assay (ELISA). Students t test showed no significant differences in the levels of either anti-CD25 IgG or anti-FOXP3 IgG between patients with breast cancer and control subjects, although patients at stage I had increased levels of anti-CD25 IgG compared with control subjects (t?=?2.11, P?=?0.037); there was no significant association of the anti-FOXP3 IgG levels with stages of breast cancer. In conclusion, circulating IgG autoantibody to CD25 instead of FOXP3 may be a potential biomarker for early diagnosis of breast cancer but further investigation remains needed to replicate this initial finding.
Related JoVE Video
Differential Accessibility of a Rotavirus VP6 Epitope in Trimers Comprising Type I, II, or III Channels as Revealed by Binding of a Human Rotavirus VP6-Specific Antibody.
J. Virol.
PUBLISHED: 10-23-2013
Show Abstract
Hide Abstract
Previous human antibody studies have shown that the human VH1-46 antibody variable gene segment encodes much of the naturally occurring human B cell response to rotavirus and is directed to virus protein 6 (VP6). It is currently unknown why some of the VH1-46-encoded human VP6 monoclonal antibodies inhibit viral transcription while others do not. In part, there are affinity differences between antibodies that likely affect inhibitory activity, but we also hypothesize that there are differing modes of binding to VP6 that affect the ability to block the transcriptional pore on double-layered particles. Here, we used a hybrid method approach for antibody epitope mapping, including single-particle cryo-electron microscopy (cryo-EM) and enhanced amide hydrogen-deuterium exchange mass spectrometry (DXMS) to determine the location and mode of binding of a VH1-46-encoded antibody, RV6-25. The structure of the RV6-25 antibody-double-layered particle (DLP) complex indicated a very complex binding pattern that revealed subtle differences in accessibility of the VP6 epitope depending on its position in the type I, II, or III channels. These subtle variations in the presentation or accessibility of the RV VP6 capsid layer led to position-specific differences in occupancy for binding of the RV6-25 antibody. The studies also showed that the location of binding of the noninhibitory antibody RV6-25 on the apical surface of RV VP6 head domain does not obstruct the transcription pore upon antibody binding, in contrast to binding of an inhibitory antibody, RV6-26, deeper in the transcriptional pore.
Related JoVE Video
Novel structural and functional insights into m3 muscarinic receptor dimer/oligomer formation.
J. Biol. Chem.
PUBLISHED: 10-16-2013
Show Abstract
Hide Abstract
Class A G protein-coupled receptors (GPCRs) are able to form homodimers and/or oligomeric arrays. We recently proposed, based on bioluminescence resonance energy transfer studies with the M3 muscarinic receptor (M3R), a prototypic class A GPCR, that the M3R is able to form multiple, structurally distinct dimers that are probably transient in nature (McMillin, S. M., Heusel, M., Liu, T., Costanzi, S., and Wess, J. (2011) J. Biol. Chem. 286, 28584-28598). To provide more direct experimental support for this concept, we employed a disulfide cross-linking strategy to trap various M3R dimeric species present in a native lipid environment (transfected COS-7 cells). Disulfide cross-linking studies were carried out with many mutant M3Rs containing single cysteine (Cys) substitutions within two distinct cytoplasmic M3R regions, the C-terminal portion of the second intracellular loop (i2) and helix H8 (H8). The pattern of cross-links that we obtained, in combination with molecular modeling studies, was consistent with the existence of two structurally distinct M3R dimer interfaces, one involving i2/i2 contacts (TM4-TM5-i2 interface) and the other one characterized by H8-H8 interactions (TM1-TM2-H8 interface). Specific H8-H8 disulfide cross-links led to significant impairments in M3R-mediated G protein activation, suggesting that changes in the structural orientation or mobility of H8 are critical for efficient receptor-G protein coupling. Our findings provide novel structural and functional insights into the mechanisms involved in M3R dimerization (oligomerization). Because the M3R shows a high degree of sequence similarity with many other class A GPCRs, our findings should be of considerable general interest.
Related JoVE Video
A novel cobalt-free, CO2-stable, and reduction-tolerant dual-phase oxygen-permeable membrane.
ACS Appl Mater Interfaces
PUBLISHED: 10-16-2013
Show Abstract
Hide Abstract
A novel CO2-stable and reduction-tolerant Ce0.8Sm0.2O(2-?)-La0.9Sr0.1FeO(3-?) (SDC-LSF) dense dual-phase oxygen-permeable membrane was designed and evaluated in this work. Homogeneous SDC-LSF composite powders for membrane fabrication were synthesized via a one-pot combustion method. The chemical compatibility and ion interdiffusion behavior between the fluorite phase SDC and perovskite phase LSF during the synthesis process was studied. The oxygen permeation flux through the dense dual-phase composite membranes was evaluated and found to be highly dependent on the volume ratio of SDC and LSF. The SDC-LSF membrane with a volume ratio of 7:3 (SDC70-LSF30) possessed the highest permeation flux, achieving 6.42 × 10(-7) mol·cm(-2)·s(-1) under an air/CO gradient at 900 °C for a 1.1-mm-thick membrane. Especially, the membrane performance showed excellent durability and operated stably without any degradation at 900 °C for 450 h with helium, CO2, or CO as the sweep gas. The present results demonstrate that a SDC70-LSF30 dual-phase membrane is a promising chemically stable device for oxygen production and CO2 capture with sufficiently high oxygen permeation flux.
Related JoVE Video
[Method for determining nitrogen dioxide in workplace air by ion-exchange chromatography].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 09-24-2013
Show Abstract
Hide Abstract
To evaluate the method for collecting NO2 in workplace air using a solid adsorbent and determining the concentration of NO2 by ion-exchange chromatography.
Related JoVE Video
Enhancing the oxygen permeation rate of Zr(0.84)Y(0.16)O(1.92)-La(0.8)Sr(0.2)Cr(0.5)Fe(0.5)O(3-?) dual-phase hollow fiber membrane by coating with Ce(0.8)Sm(0.2)O(1.9) nanoparticles.
ACS Appl Mater Interfaces
PUBLISHED: 09-24-2013
Show Abstract
Hide Abstract
Zr0.84Y0.16O1.92-La0.8Sr0.2Cr0.5Fe0.5O3-? (YSZ-LSCrF) dual-phase composite hollow fiber membranes were prepared by a combined phase-inversion and sintering method. The shell surface of the hollow fiber membrane was modified with Ce0.8Sm0.2O1.9 (SDC) via a drop-coating method. As the rate of oxygen permeation of the unmodified membrane is partly controlled by the surface exchange kinetics, coating of a porous layer of SDC on the shell side (oxygen reduction side) of the hollow fiber membrane was found to improve its oxygen permeability. Rate enhancements up to 113 and 48% were observed, yielding a maximum oxygen flux of 0.32 and 4.53 mL min(-1) cm(-2) under air/helium and air/CO gradients at 950 °C, respectively. Excess coating of SDC was found to induce significant gas phase transport limitations and hence lower the rate of oxygen permeation. A model was proposed to calculate the length of triple phase boundaries (TPBs) for the coated dual-phase composite membrane and to explain the effect of coating on the oxygen permeability.
Related JoVE Video
Super-intense white upconversion emission of Yb2O3 polycrystals and its application on luminescence converter of dye-sensitized solar cells.
Opt Lett
PUBLISHED: 08-31-2013
Show Abstract
Hide Abstract
In this Letter, we present the observation of super-intense upconversion (UC) white emission of Yb2O3 under 980 nm excitation, its evolution on excitation power density, the UC mechanism, and its application on the luminescence converter of dye-sensitized solar cells (DSSCs). It is significant to observe that Yb2O3 demonstrates at least one order more intense UC luminescence than ?-phase NaYF4:Yb3+, Er3+ and Yb2O3/DSSCs exhibit much better photovoltaic performance than ?-phase NaYF4:Yb3+, Er3+/DSSCs under strong excitation. This indicates that Yb2O3 would become a novel candidate of the solar energy converter, especially in the application of concentrator solar cells.
Related JoVE Video
Loss of NR1 subunit of NMDARs in primary sensory neurons leads to hyperexcitability and pain hypersensitivity: involvement of Ca(2+)-activated small conductance potassium channels.
J. Neurosci.
PUBLISHED: 08-16-2013
Show Abstract
Hide Abstract
It is well established that activation of NMDARs plays an essential role in spinal cord synaptic plasticity (i.e., central sensitization) and pain hypersensitivity after tissue injury. Despite prominent expression of NMDARs in DRG primary sensory neurons, the unique role of peripheral NMDARs in regulating intrinsic neuronal excitability and pain sensitivity is not well understood, in part due to the lack of selective molecular tools. To address this problem, we used Advillin-Cre driver to delete the NR1 subunit of NMDARs selectively in DRG neurons. In NR1 conditional knock-out (NR1-cKO) mice, NR1 expression is absent in DRG neurons but remains normal in spinal cord neurons; NMDA-induced currents are also eliminated in DRG neurons of these mice. Surprisingly, NR1-cKO mice displayed mechanical and thermal hypersensitivity compared with wild-type littermates. NR1-deficient DRG neurons show increased excitability, as indicated by increased frequency of action potentials, and enhanced excitatory synaptic transmission in spinal cord slices, as indicated by increased frequency of miniature EPSCs. This hyperexcitability can be reproduced by the NMDAR antagonist APV and by Ca(2+)-activated slow conductance K(+) (SK) channel blocker apamin. Furthermore, NR1-positive DRG neurons coexpress SK1/SK2 and apamin-sensitive afterhyperpolarization currents are elevated by NMDA and suppressed by APV in these neurons. Our findings reveal the hitherto unsuspected role of NMDARs in controlling the intrinsic excitability of primary sensory neurons possibly via Ca(2+)-activated SK channels. Our results also call attention to potential opposing effects of NMDAR antagonists as a treatment for pain and other neurological disorders.
Related JoVE Video
Proteomic mechanisms of cardioprotection during mammalian hibernation in woodchucks, Marmota monax.
J. Proteome Res.
PUBLISHED: 08-06-2013
Show Abstract
Hide Abstract
Mammalian hibernation is a unique strategy for winter survival in response to limited food supply and harsh climate, which includes resistance to cardiac arrhythmias. We previously found that hibernating woodchucks (Marmota monax) exhibit natural resistance to Ca2+ overload-related cardiac dysfunction and nitric oxide (NO)-dependent vasodilation, which maintains myocardial blood flow during hibernation. Since the cellular/molecular mechanisms mediating the protection are less clear, the goal of this study was to investigate changes in the heart proteome and reveal related signaling networks that are involved in establishing cardioprotection in woodchucks during hibernation. This was accomplished using isobaric tags for a relative and absolute quantification (iTRAQ) approach. The most significant changes observed in winter hibernation compared to summer non-hibernation animals were upregulation of the antioxidant catalase and inhibition of endoplasmic reticulum (ER) stress response by downregulation of GRP78, mechanisms which could be responsible for the adaptation and protection in hibernating animals. Furthermore, protein networks pertaining to NO signaling, acute phase response, CREB and NFAT transcriptional regulations, protein kinase A and ?-adrenergic signaling were also dramatically upregulated during hibernation. These adaptive mechanisms in hibernators may provide new directions to protect myocardium of non-hibernating animals, especially humans, from cardiac dysfunction induced by hypothermic stress and myocardial ischemia.
Related JoVE Video
Superior hydrogen storage and electrochemical properties of Mg(x)Ni(100-x)/Pd films at room temperature.
Dalton Trans
PUBLISHED: 08-01-2013
Show Abstract
Hide Abstract
The Mg(x)Ni(100-x) films of 100 nm have been prepared by magnetron co-sputtering Mg and Ni targets, and a Pd layer of 10 nm was deposited on these films by magnetron sputtering a Pd target. Mg2Ni and MgNi2 are directly generated during the co-sputtering process in the Mg84Ni16/Pd and Mg48Ni52/Pd films. The hydrogen storage properties of the films under 0.1 MPa H2 at 298 K were investigated. The hydrogenation of the Mg84Ni16/Pd film saturates within 45 s and exhibits the faster absorption kinetics compared with Mg94Ni6/Pd and Mg48Ni52/Pd films. The electrochemical properties of the Mg(x)Ni(100-x)/Pd films were investigated in 6 M KOH with a three-electrode cell. The Mg84Ni16/Pd film can be activated just at the first cycle. The maximum discharge capacity of the Mg84Ni16/Pd film is 482.7 mAh g(-1), the highest among these films.
Related JoVE Video
Effects of the ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate on the growth of wheat seedlings.
Environ Sci Pollut Res Int
PUBLISHED: 07-23-2013
Show Abstract
Hide Abstract
Ionic liquids (ILs) are called "green" solvents, which are due to their unique physicochemical properties and potential applications in various areas. However, the toxicity of ILs has attracted increasing attention from scientific researchers. The present paper studied the toxic effects of 1-octyl-3-methylimidazolium hexafluorophosphate ([C8mim]PF6) on wheat seedlings at 0, 1, 2, 4, 6, and 8 mg l(-1) on days 7, 10 and 13. The present results showed that the growth of wheat seedlings was seriously inhibited when the concentration was higher than 2 mg l(-1) and the inhibitory effect enhanced with increasing concentration and time. The EC50 values for germination, shoot length, root length and dry weight were 11.104, 5.187, 4.380 and 6.292 mg l(-1), respectively. [C8mim]PF6 could cause an increase in the production of ROS, which led to the oxidative damage and lipid peroxidation. Furthermore, these toxic effects on wheat seedlings were irreversible.
Related JoVE Video
Preparation and optical properties of YH2:Er2+ and Y2O3:Er3+ nanoparticles.
J Nanosci Nanotechnol
PUBLISHED: 07-19-2013
Show Abstract
Hide Abstract
The rare earth hydride nanoparticles have been prepared successfully by a novel method of hydrogen plasma-metal reaction. The YH2:Er2+ nanoparticles of 40-50 nm were polycrystalline and in hexagonal shape. The Y2O3:Er3+ nanoparticles were fabricated by annealing the hydride nanoparticles in air at 300, 500 and 700 degrees C, respectively. The influence of the sintering temperature on the size, crystal structure and optical properties of these nanoparticle samples were investigated. After annealing, the Y2O3:Er3+ nanoparticles became single crystalline and spherical shape, and the mean particle size of these particles did not change apparently upon the annealing temperature up to 700 degrees C. With the increase of the annealing temperature, the absorption intensity of YH2 in the Fourier transform infrared spectroscopy spectra decreased and the peak position moved to high-frequency, whereas the absorption intensity of Y2O3 was enhanced. The intensity of the near-IR fluorescence spectra of the Y2O3:Er3+ nanoparticles increased remarkably with the increase of the annealing temperature from 300 to 700 degrees C. The Y2O3:Er3+ sample sintered at 700 degrees C exhibited a strong photoluminescent intensity at the wavelength of about 1535 nm, with a narrow full width of 6 nm at the half maximum. This makes the Y2O3:Er3+ nanoparticles promising for the applications in the optical communication devices.
Related JoVE Video
Expression and clinical significance of livin protein in hepatocellular carcinoma.
Dis. Markers
PUBLISHED: 06-30-2013
Show Abstract
Hide Abstract
In this study, the two-step PV method of immunohistochemistry was used to determine livin protein expression in HCC tissues, pericarcinoma tissues, hepatitis/hepatic cirrhosis tissues, and normal hepatic tissues, and livin protein expression was detected in the blood plasma of patients with HCC before and after surgery, subjects with hepatic cirrhosis and hepatitis, and healthy blood donors using ELISA. Livin protein expression was significantly higher in HCC tissues than that in normal hepatic tissues and hepatitis/hepatic cirrhosis tissues, with no significant difference between HCC tissues and pericarcinoma tissues. The HCC patients with positive livin protein expression had a significantly higher survival rate than those with negative livin protein expression. Livin protein expression was significantly higher in the blood plasma of patients with HCC before and after surgery and in patients with hepatic cirrhosis and hepatitis than that in healthy blood donors, whereas livin protein expression in the blood plasma of patients with HCC was not significantly different from that of patients with hepatic cirrhosis and hepatitis. Livin protein expression in HCC tissues did not correlate with that in the blood plasma of the same HCC patients. Livin protein expression may be a potential, effective indicator for assessing prognosis in patients with HCC.
Related JoVE Video
Sustained ventricular tachycardia caused by anaphylactic reaction.
Am J Emerg Med
PUBLISHED: 06-08-2013
Show Abstract
Hide Abstract
We report a 30-year-old man who developed severe anaphylactic reactions with sustained ventricular tachycardia after eating seafood. This case emphasizes the need for cardiac monitoring in patients with anaphylaxis to identify malignant ventricular arrhythmias early.
Related JoVE Video
The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics.
Exp. Cell Res.
PUBLISHED: 06-03-2013
Show Abstract
Hide Abstract
Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109-154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics.
Related JoVE Video
Increased expression of mitotic arrest deficient-like 1 (MAD1L1) is associated with poor prognosis and insensitive to Taxol treatment in breast cancer.
Breast Cancer Res. Treat.
PUBLISHED: 05-23-2013
Show Abstract
Hide Abstract
Aneuploidy is a characteristic of human cancers, and recent studies have suggested that defects of mitotic checkpoints play a role in carcinogenesis. Mitotic Arrest Deficient-Like 1 (MAD1L1), whose altered expression is associated with chromosomal instability, is a checkpoint gene. We examined MAD1L1 protein expression from 461 breast cancer tissues and patients normal breast tissues by tissue microarray to study the correlation between the MAD1L1 expression and the clinicopathological features. MAD1L1 protein expression was significantly increased in the nuclei of cancer cells (28.4 %) compared with that in normal mammary cells (2.2 %), and was correlated with Her-2 status, cancer subtypes, p53 status, and age. High level of MAD1L1 expression in nuclei was associated with worse OS (p = 0.018). Furthermore, patients with high level of MAD1L1 expression (in nuclei) and undergone Taxol chemotherapy treatment have shorter overall survival than ones without Taxol treatment in this study (p = 0.026). In conclusion, our data demonstrated a significant correlation between nuclear expression of MAD1L1 protein and adverse prognosis in breast cancer. MAD1L1 might be used as a prognostic biomarker for breast cancer and expression of MAD1L1 in nuclei is also a predict biomarker of contraindication to pacilitaxel treatment in breast cancer.
Related JoVE Video
A quality improvement project for reducing cardiac computed tomography radiation dose in a community-based, multihospital setting.
Crit Pathw Cardiol
PUBLISHED: 05-18-2013
Show Abstract
Hide Abstract
Radiation associated with computed tomography coronary angiography (CTCA) is a persistent concern. Strategies for reducing radiation exposure have been described, primarily in academic settings. We developed a standard protocol for CTCA acquisition focused on radiation reduction strategies in a community-based, multihospital setting and hypothesized that the protocol would be effective at reducing radiation in this setting. The protocol included the use of body mass index based tube voltage adjustment and routine use of prospective electrocardiographic gating with either dose modulation or step-and-shoot acquisition. Data on radiation exposure were collected retrospectively and compared by nonparametric testing. Some hospitals failed to routinely record radiation exposure data; only 2 facilities had data available from both before and after the intervention for direct comparison. Data were acquired from 124 subjects, 41 from the standard of care group and 83 scanned under the new protocol. In hospital A, radiation was significantly reduced by 61% from 20.5 ± 4.6 millisieverts (mSv) to 7.9 ± 4.8 mSv (P < 0.001). Within the new protocol group for hospital A, radiation was lower with step-and-shoot (4.0 ± 1.5 mSv) as compared to dose modulation (10.2 ± 4.2 mSv, P < 0.001). In hospital B, which already employed step-and-shoot acquisition, radiation dose was reduced 16% from 9.3 ± 3.0 mSv to 7.9 ± 2.2 mSv (P < 0.017) by applying body mass index-based tube voltage adjustment alone. In conclusion, a minimal investment in institutional resources can result in a reduction in radiation exposure from CTCA, even in a community-based, multihospital setting. Some facilities do not routinely record radiation exposure data.
Related JoVE Video
Communication: excitation band modulation with high-order photonic band gap in PMMA:Eu(TTA)3(TPPO)2 opals.
J Chem Phys
PUBLISHED: 05-17-2013
Show Abstract
Hide Abstract
Changes in the excitation spectra of luminescent species inserted in photorefractive crystals as a function of changes in the high-order photonic band gap (PBG) have not been previously observed. In this communication, we present our results monitoring the excitation band of Eu(TTA)3(TPPO)2 inserted in the PMMA opal photonic crystals as a function of the changes in the high-order PBG of the crystals. We find shifts in the complex excitation band and changes in the integrated emission intensity that correlates with shifts in the high-order PBG through coupling to the excitation transition.
Related JoVE Video
Survivin promotion of melanoma metastasis requires upregulation of ?5 integrin.
Carcinogenesis
PUBLISHED: 05-02-2013
Show Abstract
Hide Abstract
Survivin is an apoptotic and mitotic regulator that is overexpressed in melanoma and a poor prognostic marker in patients with metastatic disease. We recently showed that Survivin enhances melanoma cell motility through Akt-dependent upregulation of ?5 integrin. However, the functional role of Survivin in melanoma metastasis is not clearly understood. We found that overexpression of Survivin in LOX and YUSAC2 human melanoma cells increased colony formation in soft agar, and this effect was abrogated by knockdown of ?5 integrin by RNA interference. We employed melanoma cell xenografts to determine the in vivo effect of Survivin overexpression on melanoma metastasis. Although Survivin overexpression did not affect primary tumor growth of YUSAC2 or LOX subcutaneous tumors, or indices of proliferation or apoptosis, it significantly increased expression of ?5 integrin in the primary tumors and formation of metastatic colonies in the lungs. Additionally, Survivin overexpression resulted in enhanced lung colony formation following intravenous (i.v.) injection of tumor cells in vivo and increased adherence to fibronectin-coated plastic in vitro. Importantly, in vivo inhibition of ?5 integrin via intraperitoneal injection of an ?5?1 integrin-blocking antibody significantly slowed tumor growth and reduced Survivin-enhanced pulmonary metastasis. Knockdown of ?5 integrin in cells prior to i.v. injection also blocked Survivin-enhanced lung colony formation. These findings support a direct role for Survivin in melanoma metastasis, which requires ?5 integrin and suggest that inhibitors of ?5 integrin may be useful in combating this process.
Related JoVE Video
Analysis of intragraft MicroRNA expression in a mouse-to-rat cardiac xenotransplantation model.
Microsurgery
PUBLISHED: 04-29-2013
Show Abstract
Hide Abstract
Xenograft rejection poses the largest obstacle to successful xenotransplantation. Recent studies have demonstrated that miRNAs play essential roles in embryogenesis, cell proliferation, and pathogenesis of human diseases. However, the role of miRNA in regulating xenograft rejection is relatively unknown. This study was undertaken to analyze the profile of intragraft miRNA expression in a heterotopic mouse-to-rat cardiac xenotransplantation model. Using microarray analysis, a total of 579 miRNAs were detected in the grafts following transplantation. When compared with syngeneic heart grafts, 24 and 25 miRNAs were found to differentially express in xenografts at 24 and 40 hours (endpoint of rejection), respectively, following transplantation. Three major miRNAs were then further analyzed, and it was found that the xenografts showed high expression of miR-146a and miR-155, but low expression of miR-451 when compared with isograft controls. This study suggests that miRNAs detected in this model are potentially involved in the xenogeneic immune response and could play an important role in regulating xenograft rejection. © 2013 Wiley Periodicals, Inc. Microsurgery 34:44-50, 2014.
Related JoVE Video
Identification of thioredoxin target protein networks in cardiac tissues of a transgenic mouse.
Methods Mol. Biol.
PUBLISHED: 04-23-2013
Show Abstract
Hide Abstract
The advent of sensitive and robust quantitative proteomics techniques has been emerging as a vital tool for deciphering complex biological puzzles that would have been challenging to conventional molecular biology methods. The method here describes the use of two isotope labeling techniques-isobaric tags for relative and absolute quantification (iTRAQ) and redox isotope-coded affinity tags (ICAT)-to elucidate the cardiovascular redox-proteome changes and thioredoxin 1 (Trx1)-regulated protein network in cardiac-specific Trx1 transgenic mouse models. The strategy involves the use of an amine-labeling iTRAQ technique, gauging the global proteome changes in Trx1 transgenic mice at the protein level, while ICAT, labeling redox-sensitive cysteines, reveals the redox status of cysteine residues. Collectively, these two quantitative proteomics techniques can not only quantify global changes of the cardiovascular proteome but also pinpoint specific redox-sensitive cysteine sites that are subjected to Trx1-catalyzed reduction.
Related JoVE Video
New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms?
Pflugers Arch.
PUBLISHED: 04-14-2013
Show Abstract
Hide Abstract
Itch and pain are closely related but distinct sensations. They share largely overlapping mediators and receptors, and itch-responding neurons are also sensitive to pain stimuli. Itch-mediating primary sensory neurons are equipped with distinct receptors and ion channels for itch transduction, including Mas-related G protein-coupled receptors (Mrgprs), protease-activated receptors, histamine receptors, bile acid receptor, toll-like receptors, and transient receptor potential subfamily V1/A1 (TRPV1/A1). Recent progress has indicated the existence of an itch-specific neuronal circuitry. The MrgprA3-expressing primary sensory neurons exclusively innervate the epidermis of skin, and their central axons connect with gastrin-releasing peptide receptor (GRPR)-expressing neurons in the superficial spinal cord. Notably, ablation of MrgprA3-expressing primary sensory neurons or GRPR-expressing spinal cord neurons results in selective reduction in itch but not pain. Chronic itch results from dysfunction of the immune and nervous system and can manifest as neural plasticity despite the fact that chronic itch is often treated by dermatologists. While differences between acute pain and acute itch are striking, chronic itch and chronic pain share many similar mechanisms, including peripheral sensitization (increased responses of primary sensory neurons to itch and pain mediators), central sensitization (hyperactivity of spinal projection neurons and excitatory interneurons), loss of inhibitory control in the spinal cord, and neuro-immune and neuro-glial interactions. Notably, painful stimuli can elicit itch in some chronic conditions (e.g., atopic dermatitis), and some drugs for treating chronic pain are also effective in chronic itch. Thus, itch and pain have more similarities in pathological and chronic conditions.
Related JoVE Video
Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2.
Nat. Med.
PUBLISHED: 04-12-2013
Show Abstract
Hide Abstract
Here we show that Mst1, a proapoptotic kinase, impairs protein quality control mechanisms in the heart through inhibition of autophagy. Stress-induced activation of Mst1 in cardiomyocytes promoted accumulation of p62 and aggresome formation, accompanied by the disappearance of autophagosomes. Mst1 phosphorylated the Thr108 residue in the BH3 domain of Beclin1, which enhanced the interaction between Beclin1 and Bcl-2 and/or Bcl-xL, stabilized the Beclin1 homodimer, inhibited the phosphatidylinositide 3-kinase activity of the Atg14L-Beclin1-Vps34 complex and suppressed autophagy. Furthermore, Mst1-induced sequestration of Bcl-2 and Bcl-xL by Beclin1 allows Bax to become active, thereby stimulating apoptosis. Mst1 promoted cardiac dysfunction in mice subjected to myocardial infarction by inhibiting autophagy, associated with increased levels of Thr108-phosphorylated Beclin1. Moreover, dilated cardiomyopathy in humans was associated with increased levels of Thr108-phosphorylated Beclin1 and signs of autophagic suppression. These results suggest that Mst1 coordinately regulates autophagy and apoptosis by phosphorylating Beclin1 and consequently modulating a three-way interaction among Bcl-2 proteins, Beclin1 and Bax.
Related JoVE Video
Three-dimensional structure and biophysical characterization of Staphylococcus aureus cell surface antigen-manganese transporter MntC.
J. Mol. Biol.
PUBLISHED: 04-11-2013
Show Abstract
Hide Abstract
MntC is a metal-binding protein component of the Mn²?-specific mntABC transporter from the pathogen Staphylococcus aureus. The protein is expressed during the early stages of infection and was proven to be effective at reducing both S. aureus and Staphylococcus epidermidis infections in a murine animal model when used as a vaccine antigen. MntC is currently being tested in human clinical trials as a component of a multiantigen vaccine for the prevention of S. aureus infections. To better understand the biological function of MntC, we are providing structural and biophysical characterization of the protein in this work. The three-dimensional structure of the protein was solved by X-ray crystallography at 2.2Å resolution and suggests two potential metal binding modes, which may lead to reversible as well as irreversible metal binding. Precise Mn²?-binding affinity of the protein was determined from the isothermal titration calorimetry experiments using a competition approach. Differential scanning calorimetry experiments confirmed that divalent metals can indeed bind to MntC reversibly as well as irreversibly. Finally, Mn²?-induced structural and dynamics changes have been characterized using spectroscopic methods and deuterium-hydrogen exchange mass spectroscopy. Results of the experiments show that these changes are minimal and are largely restricted to the structural elements involved in metal coordination. Therefore, it is unlikely that antibody binding to this antigen will be affected by the occupancy of the metal-binding site by Mn²?.
Related JoVE Video
Coexistence of non-functional ectopic thyroid tissue and a normal thyroid: A case report.
Exp Ther Med
PUBLISHED: 04-10-2013
Show Abstract
Hide Abstract
The aim of this study was to report a rare case of non-functional ectopic thyroid tissue in the neck with a coexisting normal thyroid. A 36-year-old female presented with a mass in the anterior neck. The thyroid function of the patient was normal. Ultrasonography and computed tomography (CT) revealed a normal thyroid gland and a solid mass in the middle lower neck. Scintigraphy showed a normal thyroid and the mass did show any uptake of (99m)TcO4(-) . The patient underwent en bloc resection. During surgery, the mass was observed to be well encapsulated and completely separated from the thyroid gland. Histology revealed it as ectopic thyroid tissue. The patient had an uneventful recovery.
Related JoVE Video
Systematic review and meta-analysis of chronic kidney disease as predictor of atrial fibrillation recurrence following catheter ablation.
Cardiol J
PUBLISHED: 04-07-2013
Show Abstract
Hide Abstract
Recent observational studies have shown that patients with chronic kidney disease (CKD) have higher risk of atrial fibrillation (AF) recurrence and therefore the value of catheter ablation therapy in patients with CKD has been doubted. The purpose of this meta-analysis was to systematically analyze the effect of CKD on recurrence of AF following catheter ablation.
Related JoVE Video
Diagnostic validity of human papillomavirus E6/E7 mRNA test in cervical cytological samples.
J. Virol. Methods
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
Human papillomavirus (HPV) DNA tests tend to show high sensitivity, but poor specificity in detecting high-grade cervical lesions. This study aimed to explore the clinical performance of QuantiVirus(®) HPV E6/E7 mRNA in identifying ?Grade 2 cervical intraepithelial neoplasia. Thin-prep(®) liquid based cytology test (LBC) samples were collected from October 2009 to October 2011 from women who underwent outpatient hospital-based gynecological screening. LBC samples were processed for E6/E7 mRNA detection and HPV DNA detection. Of 335 patients, 135 (40.3%) were HPV E6/E7 mRNA positive for high-risk HPV subtypes. The positivity rate of HPV E6/E7 mRNA increased with the severity of cytological and histological evaluation. An optimal cut-off value of ?567copies/ml was determined using receiver operating characteristic (ROC) curve, and positive predictive value and negative predictive value of cut-off value (?567copies/ml) were higher than those of E6/E7 mRNA positivity only, but not significant. QuantiVirus(®) HPV E6/E7 mRNA testing may be a valuable tool in triage for identifying ?Grade 2 cervical intraepithelial neoplasia. A high specificity and a low positivity rate of E6/E7mRNA testing as a triage test in HPV DNA-positive women can be translated into a low referral for colposcopy. Studies composed of large population-based samples of women and with rigorous disease ascertainment, are needed to establish the optimal cut-off point based on ROC curve analysis.
Related JoVE Video
Polyester modification of the mammalian TRPM8 channel protein: implications for structure and function.
Cell Rep
PUBLISHED: 01-14-2013
Show Abstract
Hide Abstract
The TRPM8 ion channel is expressed in sensory neurons and is responsible for sensing environmental cues, such as cold temperatures and chemical compounds, including menthol and icilin. The channel functional activity is regulated by various physical and chemical factors and is likely to be preconditioned by its molecular composition. Our studies indicate that the TRPM8 channel forms a structural-functional complex with the polyester poly-(R)-3-hydroxybutyrate (PHB). We identified by mass spectrometry a number of PHB-modified peptides in the N terminus of the TRPM8 protein and in its extracellular S3-S4 linker. Removal of PHB by enzymatic hydrolysis and site-directed mutagenesis of both the serine residues that serve as covalent anchors for PHB and adjacent hydrophobic residues that interact with the methyl groups of the polymer resulted in significant inhibition of TRPM8 channel activity. We conclude that the TRPM8 channel undergoes posttranslational modification by PHB and that this modification is required for its normal function.
Related JoVE Video
Expression and significance of microRNA-183 in hepatocellular carcinoma.
ScientificWorldJournal
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
In our previous study, we found that some miRNAs were deregulated in hepatocellular carcinoma (HCC), including miR-183. However, the expression of miR-183 in the progression of benign liver diseases to HCC and its correlation with clinicopathologic factors remain undefined.
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.