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.
Interleukin-33 promotes disease progression in patients with primary biliary cirrhosis.
Tohoku J. Exp. Med.
PUBLISHED: 11-18-2014
Show Abstract
Hide Abstract
Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease that can cause a series of complications, including cirrhosis, liver failure and hepatocellular carcinoma. Interleukin-33 (IL-33) is expressed in various non-hematopoietic cells and a certain population of immune cells, and exerts its biological effects by binding to the specific receptor, suppression of tumorigenicity 2 (ST2). A soluble form of ST2 (sST2) has been postulated to act as a decoy receptor for IL-33. In this study, we aimed to investigate the role of IL-33 in the pathogenesis of PBC. The study included 20 healthy controls and 68 patients with PBC. We thus found the increased serum IL-33 levels in PBC patients. Its elevated levels were positively correlated with serum alkaline phosphatase levels (a key parameter for the definition of PBC) and with Child-Pugh scores, which were used to determine the prognosis of liver cirrhosis. Moreover, the serum concentrations of sST2 were significantly higher in PBC patients compared with healthy subjects, irrespective of the disease severity. Importantly, the cells that express IL-33 and/or myeloperoxidase (a marker for neutrophils) were accumulated in the livers of PBC patients, and their number increased with the severity of liver lesions. Lastly, in vitro chemotaxis assays revealed that IL-33 enhanced the migration of neutrophils. These data suggest that IL-33 may affect the progress of PBC by recruiting neutrophils to the liver. This expanded knowledge of IL-33 in PBC patients is important for developing therapeutic strategies (e.g., neutralization of IL-33), selecting optimal clinical management, and predicting prognosis.
Related JoVE Video
Hormonal receptors and vascular endothelial growth factor in juvenile nasopharyngeal angiofibroma: immunohistochemical and tissue microarray analysis.
Acta Otolaryngol.
PUBLISHED: 11-12-2014
Show Abstract
Hide Abstract
Abstract Conclusion: This work demonstrated that juvenile nasopharyngeal angiofibromas (JNAs) express high levels of hormone receptors and vascular endothelial growth factor (VEGF) compared with normal nasal mucosa. The interaction between hormone receptors and VEGF may be involved in the initiation and growth of JNA. Objectives: JNA is a rare benign tumor that occurs almost exclusively in male adolescents. Although generally regarded as a hormone-dependent tumor, this has not been proven in previous studies. The aim of this study was to investigate the role of hormone receptors in JNA and the relationship with clinical characteristics. Methods: Standard immunohistochemical microarray analysis was performed on 70 JNA samples and 10 turbinate tissue samples. Specific antibodies for androgen receptor (AR), estrogen receptor-? (ER-?), estrogen receptor-? (ER-?), progesterone receptor (PR), and VEGF were examined, and the relationships of receptor expression with age, tumor stage, and bleeding were evaluated. Results: Results showed that JNA expressed ER-? (92.9%), ER-? (91.4%), AR (65.7%), PR (12.8%), and VEGF (95.7%) at different levels. High level of VEGF was linked to elevated ER-? and ER-?. There was no significant relationship between hormonal receptors and age at diagnosis, tumor stage or bleeding. However, overexpression of ER-? was found to be an indicator of poor prognosis (p = 0.031).
Related JoVE Video
PubAngioGen: a database and knowledge for angiogenesis and related diseases.
Nucleic Acids Res.
PUBLISHED: 11-11-2014
Show Abstract
Hide Abstract
Angiogenesis is the process of generating new blood vessels based on existing ones, which is involved in many diseases including cancers, cardiovascular diseases and diabetes mellitus. Recently, great efforts have been made to explore the mechanisms of angiogenesis in various diseases and many angiogenic factors have been discovered as therapeutic targets in anti- or pro-angiogenic drug development. However, the resulted information is sparsely distributed and no systematical summarization has been made. In order to integrate these related results and facilitate the researches for the community, we conducted manual text-mining from published literature and built a database named as PubAngioGen (http://www.megabionet.org/aspd/). Our online application displays a comprehensive network for exploring the connection between angiogenesis and diseases at multilevels including protein-protein interaction, drug-target, disease-gene and signaling pathways among various cells and animal models recorded through text-mining. To enlarge the scope of the PubAngioGen application, our database also links to other common resources including STRING, DrugBank and OMIM databases, which will facilitate understanding the underlying molecular mechanisms of angiogenesis and drug development in clinical therapy.
Related JoVE Video
One-Step Click Engineering Considerably Ameliorates the Practicality of an Unqualified Rhodamine Probe.
ACS Appl Mater Interfaces
PUBLISHED: 11-08-2014
Show Abstract
Hide Abstract
This study describes the exploitation of click chemistry in the one-step molecular engineering of an unqualified rhodamine probe, leading to its considerable functional enhancement in terms of water solubility, ion selectivity, and usefulness in detecting biological and environmental samples. A dipropargyl rhodamine dye previously identified as an unselective and poorly water-soluble mercury(II) probe was used to couple with an azido polyethylene glycol (PEG) by the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition click reaction in almost quantitative yield. The simple click-engineered rhodamine probe shows, remarkably, better water solubility and mercury(II) selectivity comparing to the raw counterpart, and can be used to sensitively image mercury ions internalized by live cells and to accurately quantify the ion spiked in river water specimens. This study provides insights into the simple functional improvement of unqualified molecular dye probes via the efficient "click engineering".
Related JoVE Video
Tissue Engineering of Human Nasal Alar Cartilage Precisely by Using 3D Print.
Plast. Reconstr. Surg.
PUBLISHED: 10-31-2014
Show Abstract
Hide Abstract
Tissue engineering strategies holds promise for the restoration of damaged cartilage. However, the results of most studies are irregularly shaped beads of cartilage, which are not precise enough. Thus a precisely three-dimensional shape of cartilage graft must be taken into consideration to achieve cosmetic contour. The goal of this study was to develop a simple method to create a precisely predetermined nasal alar shape with the aid of 3D print.
Related JoVE Video
7,8-Secolignans from the fruits of Schisandra neglecta.
J Asian Nat Prod Res
PUBLISHED: 10-31-2014
Show Abstract
Hide Abstract
Two new 7,8-secolignans, neglectahenols E and F (1 and 2), together with four known 7,8-secolignans (3-6), were isolated from the fruits of Schisandra neglecta. The structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-6 were tested for their anti-tobacco mosaic virus (anti-TMV) activities at the concentration of 20 ?M. Compounds 1 and 6 showed high anti-TMV activities with inhibition rates of 38.2% and 32.7%, respectively. These rates are higher than that of a positive control. Compounds 2-5 also showed modest anti-TMV activities with inhibition rates in the range of 22.8-28.7%. These rates are close to that of a positive control.
Related JoVE Video
Degradation of polycyclic aromatic hydrocarbons in crumb tyre rubber catalysed by rutile TiO2 under UV irradiation.
Environ Technol
PUBLISHED: 10-18-2014
Show Abstract
Hide Abstract
The polycyclic aromatic hydrocarbons (PAHs) in crumb tyre rubber were firstly degraded under UV irradiation in the presence of rutile TiO2 and hydrogen peroxide. The effects of light intensity, catalyst amount, oxidant amount, initial pH value, co-solvent content, and reaction time on degradation efficiency of typical PAHs in crumb tyre rubber were studied. The results indicated that UV irradiation, rutile TiO2, and hydrogen peroxide were beneficial to the degradation of PAHs and co-solvent could accelerate the desorption of PAHs from crumb tyre rubber. Up to 90% degradation efficiency of total 16 PAHs could be obtained in the presence of rutile TiO2 (1?wt%) and hydrogen peroxide (1.0?mL) under 1800?µW?cm(-2) UV irradiation for 48?h. The high molecular weight PAHs (such as benz(a)pyrene) were more difficult to be degraded than low molecular weight PAHs (such as phenanthrene, chrysene). Moreover, through the characterization of reaction solution and degradation products via GC-MS, it was proved that the PAHs in crumb tyre rubber were successfully degraded.
Related JoVE Video
Cardiac valve cells and their microenvironment-insights from in vitro studies.
Nat Rev Cardiol
PUBLISHED: 10-14-2014
Show Abstract
Hide Abstract
During every heartbeat, cardiac valves open and close coordinately to control the unidirectional flow of blood. In this dynamically challenging environment, resident valve cells actively maintain homeostasis, but the signalling between cells and their microenvironment is complex. When homeostasis is disrupted and the valve opening obstructed, haemodynamic profiles can be altered and lead to impaired cardiac function. Currently, late stages of cardiac valve diseases are treated surgically, because no drug therapies exist to reverse or halt disease progression. Consequently, investigators have sought to understand the molecular and cellular mechanisms of valvular diseases using in vitro cell culture systems and biomaterial scaffolds that can mimic the extracellular microenvironment. In this Review, we describe how signals in the extracellular matrix regulate valve cell function. We propose that the cellular context is a critical factor when studying the molecular basis of valvular diseases in vitro, and one should consider how the surrounding matrix might influence cell signalling and functional outcomes in the valve. Investigators need to build a systems-level understanding of the complex signalling network involved in valve regulation, to facilitate drug target identification and promote in situ or ex vivo heart valve regeneration.
Related JoVE Video
Quantum-dot-tagged photonic crystal beads for multiplex detection of tumor markers.
Chem. Commun. (Camb.)
PUBLISHED: 10-13-2014
Show Abstract
Hide Abstract
Novel quantum-dot-tagged photonic crystal beads were fabricated for multiplex detection of tumor markers via self-assembly of quantum dot-embedded polystyrene nanospheres into photonic crystal beads through a microfluidic device.
Related JoVE Video
Regulation of NADPH-dependent Nitric Oxide and reactive oxygen species signalling in endothelial and melanoma cells by a photoactive NADPH analogue.
Oncotarget
PUBLISHED: 10-10-2014
Show Abstract
Hide Abstract
Nitric Oxide (NO) and Reactive oxygen species (ROS) are endogenous regulators of angiogenesis-related events as endothelial cell proliferation and survival, but NO/ROS defect or unbalance contribute to cancers. We recently designed a novel photoactive inhibitor of NO-Synthases (NOS) called NS1, which binds their NADPH site in vitro. Here, we show that NS1 inhibited NO formed in aortic rings. NS1-induced NO decrease led to an inhibition of angiogenesis in a model of VEGF-induced endothelial tubes formation. Beside this effect, NS1 reduced ROS levels in endothelial and melanoma A375 cells and in aorta. In metastatic melanoma cells, NS1 first induced a strong decrease of VEGF and blocked melanoma cell cycle at G2/M. NS1 decreased NOX4 and ROS levels that could lead to a specific proliferation arrest and cell death. In contrast, NS1 did not perturb melanocytes growth. Altogether, NS1 revealed a possible cross-talk between eNOS- and NOX4 -associated pathways in melanoma cells via VEGF, Erk and Akt modulation by NS1 that could be targeted to stop proliferation. NS1 thus constitutes a promising tool that modulates NO and redox stresses by targeting and directly inhibiting eNOS and, at least indirectly, NADPH oxidase(s), with great potential to control angiogenesis.
Related JoVE Video
High Divergence of the Precursor Peptides in Combinatorial Lanthipeptide Biosynthesis.
ACS Chem. Biol.
PUBLISHED: 10-02-2014
Show Abstract
Hide Abstract
Lanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and post-translationally modified peptides (RiPPs). These compounds are widely distributed in taxonomically distant species, and their biosynthetic systems and biological activities are diverse. A unique example of lanthipeptide biosynthesis is the prochlorosin synthetase ProcM from the marine cyanobacterium Prochlorococcus MIT9313, which transforms up to 29 different precursor peptides (ProcAs) into a library of lanthipeptides called prochlorosins (Pcns) with highly diverse sequences and ring topologies. Here, we show that many ProcM-like enzymes from a variety of bacteria have the capacity to carry out post-translational modifications on highly diverse precursor peptides, providing new examples of natural combinatorial biosynthesis. We also demonstrate that the leader peptides come from different evolutionary origins, suggesting that the combinatorial biosynthesis is tied to the enzyme and not a specific type of leader peptide. For some precursor peptides encoded in the genomes, the leader peptides apparently have been truncated at the N-termini, and we show that these N-terminally truncated peptides are still substrates of the enzymes. Consistent with this hypothesis, we demonstrate that about two-thirds of the ProcA N-terminal sequence is not essential for ProcM activity. Our results also highlight the potential of exploring this class of natural products by genome mining and bioengineering.
Related JoVE Video
Effects of pharmaceutical PEGylation on drug metabolism and its clinical concerns.
Expert Opin Drug Metab Toxicol
PUBLISHED: 09-30-2014
Show Abstract
Hide Abstract
PEGylation refers to covalent conjugation of one or more polyethylene glycol chains to a drug molecule. It also refers to formulation of a drug into PEGylated drug-delivery vehicles in pharmacy. It is well-known that PEGylation can greatly influence the pharmacokinetics and pharmacodynamics of drugs.
Related JoVE Video
Big effects of small RNAs on legume root biotic interactions.
Genome Biol.
PUBLISHED: 09-24-2014
Show Abstract
Hide Abstract
Comprehensive profiling of microRNAs (miRNAs) from the legume Medicago truncatula reveals the organization of miRNA-based regulatory modules in root biotic interactions.
Related JoVE Video
Glucuronidation of capsaicin by liver microsomes and expressed UGT enzymes: reaction kinetics, contribution of individual enzymes and marked species differences.
Expert Opin Drug Metab Toxicol
PUBLISHED: 09-16-2014
Show Abstract
Hide Abstract
The objectives of this study are to characterize capsaicin glucuronidation using liver microsomes and to determine the contribution of individual UDP-glucuronosyltransferase (UGT) enzymes to hepatic glucuronidation of capsaicin.
Related JoVE Video
Pelvic pain from a giant presacral Tarlov cyst successfully obliterated using aneurysm clips in a patient with Marfan syndrome.
J Neurosurg Spine
PUBLISHED: 09-12-2014
Show Abstract
Hide Abstract
Patients with Marfan syndrome used to succumb early in life from cardiovascular complications. With the current rapid advance in medical and surgical care, such patients may now have near-normal longevities. Consequently, rare late-life complications are emerging in these patients and represent challenges to clinicians for their diagnoses and treatments. The authors report a rare case of pelvic pain and genital prolapse from a giant presacral Tarlov cyst in a 67-year-old patient with Marfan syndrome. This 67-year-old Caucasian female presented with progressively severe pelvic pain, intermittent explosive diarrhea, and dysuria. Physical and bimanual examination demonstrated genital prolapse and a nontender, cyst-like mass fixed in the midline. She underwent ultrasound, CT, and eventually MRI evaluations that led to the diagnosis of a giant (6.7 × 6.4 × 6.6 cm) Tarlov cyst originating from the right S-2 nerve root sleeve/sacral foramen with intrapelvic extension. She underwent S1-S2 and S2-S3 laminectomy with obliteration of the Tarlov cyst using aneurysm clips. Postoperatively, her pelvic pain and bowel symptoms resolved and the bladder symptoms improved. The 3-month follow-up CT of abdomen/pelvis demonstrated resolution of the cyst. The present case illustrates that clinicians caring for elderly patients with Marfan syndrome need to increasingly recognize such unusual late-life complications. Also, these large Tarlov cysts can be simply and effectively obliterated with aneurysm clips.
Related JoVE Video
Design and evaluation of injectable niclosamide nanocrystals prepared by wet media milling technique.
Drug Dev Ind Pharm
PUBLISHED: 09-11-2014
Show Abstract
Hide Abstract
Abstract Niclosamide is an anthelmintic drug that also demonstrates great potential in fighting against cancers. However, parenteral delivery of niclosamide is challenged due to its insoluble property. This study aimed to develop an injectable formulation for niclosamide using nanocrystals. Niclosamide nanocrystals were prepared by wet media milling technique and characterized by electronic microscopes, differential scanning calorimetry, powder X-ray diffractometry and drug release, etc. The resulting nanocrystals using Tween 80 as the stabilizer were approximately 235?nm in particle size and showed a satisfactory stability. Pharmacokinetic studies revealed that there was no significant difference in plasma concentration-time profiles between nanocrystals and the control formulation (i.e. drug solution). By contrast, a significant difference in tissue distribution was observed at 2?h. Further, niclosamide nanocrystals presented a comparable antitumor effect to the drug solution against EC9076 cell line. We concluded that the nanocrystal formulation with solution-like behaviors should be a promising choice for intravenous delivery of niclosamide.
Related JoVE Video
Synthesis and reactivity of new aminophenolate complexes of nickel.
Molecules
PUBLISHED: 09-02-2014
Show Abstract
Hide Abstract
New well-defined, paramagnetic nickel complexes have been prepared and characterized by X-ray crystallography. The complexes were found to be active for the cross-coupling of alkyl electrophiles (especially ethyl 2-bromobutyrate) with alkyl Grignard reagents. The ligand architecture in these new complexes could potentially be rendered chiral, opening up future possibilities for performing asymmetric cross-coupling reactions.
Related JoVE Video
Electrochemical immunosensor for ?-fetoprotein detection using ferroferric oxide and horseradish peroxidase as signal amplification labels.
Anal. Biochem.
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
An electrochemical immunosensor for quantitative detection of ?-fetoprotein (AFP) in human serum was developed using graphene sheets (GS) and thionine (TH) as electrode materials and mesoporous silica nanoparticles (MSNs) loaded with ferroferric oxide (Fe3O4) nanoparticles and horseradish peroxidase (HRP) as labels for signal amplification. In this study, the compound of GS and TH (GS-TH) was used as a substrate for promoting electron transfer and immobilization of primary antibody of AFP (Ab1). MSNs were used as a carrier for immobilization of secondary antibody of AFP (Ab2), Fe3O4, and HRP. The synergistic effect occurred between Fe3O4 and HRP and greatly improved the sensitivity of the immunosensor. This method could detect AFP over a wide concentration range from 0.01 to 25ngml(-1) with a detection limit of 4pgml(-1). This strategy may find wide potential application in clinical analysis or detection of other tumor markers.
Related JoVE Video
Hepatoma-selective imaging of heavy metal ions using a 'clicked' galactosylrhodamine probe.
Chem. Commun. (Camb.)
PUBLISHED: 08-22-2014
Show Abstract
Hide Abstract
This study depicts the 'click' construction of a water-soluble galactosyl rhodamine that can selectively probe mercury ions internalized by hepatoma cells over other cancer cells.
Related JoVE Video
Towards High Water Permeability in Triazine-Framework-Based Microporous Membranes for Dehydration of Ethanol.
ChemSusChem
PUBLISHED: 08-19-2014
Show Abstract
Hide Abstract
The microstructural evolution of a series of triazine framework-based microporous (TFM) membranes under different conditions has been explored in this work. The pristine TFM membrane is in?situ fabricated in the course of polymer synthesis via a facile Brønsted-acid-catalyzed cyclotrimerizaiton reaction. The as-synthesized polymer exhibits a microporous network with high thermal stability. The free volume size of the TFM membranes gradually evolved from a unimodal distribution to a bimodal distribution under annealing, as analyzed by positron annihilation lifetime spectroscopy (PALS). The emergence of the bimodal distribution is probably ascribed to the synergetic effect of quenching and thermal cyclization reaction. In addition, the fractional free volume (FFV) of the membranes presents a concave trend with increasing annealing temperature. Vapor sorption tests reveal that the mass transport properties are closely associated with the free volume evolution, which provides an optimal condition for dehydration of biofuels. A promising separation performance with extremely high water permeability has been attained for dehydration of an 85?wt?% ethanol aqueous solution at 45?°C. The study on the free volume evolution of the TFM membranes may provide useful insights about the microstructure and mass transport behavior of the microporous polymeric materials.
Related JoVE Video
[Comparison and analysis between CLL-hBMSC and N-hBMSC].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 08-19-2014
Show Abstract
Hide Abstract
This study was purposed to compare and analyze the chronic lymphocytic leukemia human bone marrow stromal cells (CLL-hBMSC) and normal hBMSC (N-hBMSC) so as to provide theoretical evidence for establishment of CLL-hBMSC interaction model to imitate CLL microenvironment. Mononuclear cells (MNC) were isolated from bone marrow of CLL patients and healthy donors and then were cultured, hBMSC were established by expanding for at least five passages. The mRNA expression of adhesion molecules, such as vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), was analyzed by real-time PCR. The mRNA and protein expression of lymphotoxin beta receptor (LT?R) were determined by real-time PCR and Western blot, respectively. The individual NF-?B members at protein level of CLL-hBMSC and N-hBMSC were examined by Western blot. The effect of LT?1?2 on individual NF-?B family members at protein level in CLL-hBMSC and N-hBMSC was also examined by Western blot. The death of CLL cells was determined by flow cytometry with PI staining when cultured with or without CLL-hBMSC and N-hBMSC at different time points. The results showed that the hBMSC could be established successfully from bone marrow of CLL patients, which were similar to N-hBMSC. Adhesion molecules, such as VCAM-1 and ICAM-1, were found to be expressed at similar mRNA levels in CLL-hBMSC and N-hBMSC. LT?R expressions at mRNA and protein levels were comparable between CLL-hBMSC and N-hBMSC. The protein expression of the individual NF-?B family members could be detected in CLL-hBMSC and N-hBMSC with similar expression levels. LT?1?2 stimulation activated both the classical ( RelA/p50 ) and alternative ( RelB/p52 ) NF-?B complexes in CLL-hBMSC and N-hBMSC. The capacities of CLL-hBMSC and N-hBMSC to protect CLL cell survival were similar. It is concluded that there is no statistical difference between bone marrow from healthy donors and CLL patients in the efficiency of generating of hBMSC. LT?R-NF-?B signaling molecules are expressed and activated on hBMSC with a similar pattern.
Related JoVE Video
Novel and facile method, dynamic self-assemble, to prepare SnO?/rGO droplet aerogel with complex morphologies and their application in supercapacitors.
ACS Appl Mater Interfaces
PUBLISHED: 08-18-2014
Show Abstract
Hide Abstract
A facile and novel method to prepare SnO2/reduced graphene oxide (rGO) droplet aerogels with complex morphologies had been developed. This method has been named dynamic self-assemble. Aerogels with both "egg-tart" and "mushroom" shapes were obtained by this method. The changes in the graphene oxide (GO) droplet morphologies during the dynamic process of a GO droplet falling into a SnCl2 target solution were monitored using a high speed camera. The formed SnO2/rGO aerogels were then characterized by Raman spectroscopy, thermogravimetric analysis, X-ray diffraction analysis, and X-ray photoelectron spectroscopy. The microstructures of the SnO2/rGO aerogels were observed with scanning electron microscopy and transmission electron microscopy. Finally, the SnO2/rGO droplet aerogels were used as the electrode material in a symmetrical two-electrode supercapacitor and the electrochemical performance of the supercapacitor was investigated using cyclic voltammetry and galvanostatic charge/discharge methods. The SnO2/rGO electrodes demonstrated excellent electrochemical performance and stability. At a scan rate of 5 mV/s, their highest gravimetric and volumetric specific capacitances were 310 F/g and 180 F/cm(3), respectively, and their energy and power densities were as high as 30 Wh·kg(-1) and 8.3 kW·kg(-1), respectively.
Related JoVE Video
[The protective effect of valproic acid on myocardium in rats with lethal scald injury and its mechanism].
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
PUBLISHED: 08-16-2014
Show Abstract
Hide Abstract
To investigate the protective effects of valproic acid (VPA) on myocardium in rats following lethal burn injury and its mechanism.
Related JoVE Video
Sulfur copolymer nanowires with enhanced visible-light photoresponse.
Chem. Commun. (Camb.)
PUBLISHED: 08-12-2014
Show Abstract
Hide Abstract
Sulfur copolymer nanowires have been reported for the first time as highly stable visible-light-active photocatalysts for photoelectrochemical water splitting depending on their size and sulfur content. The as-prepared sulfur copolymer nanowires can serve as a sulfur source and templates to create metal sulfide/copolymer heterocatalysts.
Related JoVE Video
Anatomical study of insula and its relationship with the adjacent structures.
J Craniofac Surg
PUBLISHED: 08-08-2014
Show Abstract
Hide Abstract
Insular lobe is folded deep in the sylvian fissure, and the transsylvian transinsular approach is one of the most commonly used methods for lesions in the insula, basal ganglia, amygdala, and hippocampus. Hence, it is essential for surgeons to master a specific anatomic knowledge of the insula and its adjacent structures. This study aims to locate the insula, measure relevant parameters, and reduce the occurrence of surgical injury and postoperative complications.
Related JoVE Video
Structural investigation of ribosomally synthesized natural products by hypothetical structure enumeration and evaluation using tandem MS.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-04-2014
Show Abstract
Hide Abstract
Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a growing class of natural products that are found in all domains of life. These compounds possess vast structural diversity and have a wide range of biological activities, promising a fertile ground for exploring novel natural products. One challenging aspect of RiPP research is the difficulty of structure determination due to their architectural complexity. We here describe a method for automated structural characterization of RiPPs by tandem mass spectrometry. This method is based on the combined analysis of multiple mass spectra and evaluation of a collection of hypothetical structures predicted based on the biosynthetic gene cluster and molecular weight. We show that this method is effective in structural characterization of complex RiPPs, including lanthipeptides, glycopeptides, and azole-containing peptides. Using this method, we have determined the structure of a previously structurally uncharacterized lanthipeptide, prochlorosin 1.2, and investigated the order of the posttranslational modifications in three biosynthetic systems.
Related JoVE Video
Fluoride Affects Calcium Homeostasis and Osteogenic Transcription Factor Expressions Through L-type Calcium Channels in Osteoblast Cell Line.
Biol Trace Elem Res
PUBLISHED: 07-30-2014
Show Abstract
Hide Abstract
Osteoblast L-type voltage-dependent calcium channels (VDCC) play important roles in maintaining intracellular homeostasis and influencing multiple cellular processes. In particular, they contribute to the activities and functions of osteoblasts (OBs). In order to study how L-type VDCC modulate calcium ion (Ca(2+)) homeostasis and the expression of osteogenic transcription factors in OBs exposed to fluoride, MC3T3-E1 cells were exposed to a gradient of concentrations of fluoride (0, 2.0, 5.0, 10.0 mg/L) in combination with 10 ?M nifedipine, a specific inhibitor of VDCC, for 48 h. We examined messenger RNA (mRNA) and protein levels of Cav1.2, the main subunit of VDCC, and c-fos, c-jun, runt-related transcription factor 2 (Runx2), osterix (OSX), and intracellular free Ca(2+) ([Ca(2+)]i) concentrations in MC3T3-E1 cells. Our results showed that [Ca(2+)]i levels increased in a dose-dependent manner with increase in concentration of fluoride. Meantime, results indicated that lower concentrations of fluoride (less than 5 mg/L, especially 2 mg/L) can lead to high expression of Cav1.2 and enhance osteogenic function, while high concentration of fluoride (10 mg/L) can induce decreased Cav1.2 and osteogenic transcriptional factors in MC3T3E1 cells exposed to fluoride. However, the levels of [Ca(2+)]i, Cav1.2, c-fos, c-jun, Runx2, and OSX induced by fluoride were significantly altered and even reversed in the presence of nifedipine. These results demonstrate that L-type calcium channels play a crucial role in Ca(2+) homeostasis and they affect the expression of osteogenic transcription factors in fluoride-treated osteoblasts.
Related JoVE Video
Evolution of physiological responses to salt stress in hexaploid wheat.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-29-2014
Show Abstract
Hide Abstract
Hexaploid bread wheat (Triticum aestivum L., genome BBAADD) is generally more salt tolerant than its tetraploid wheat progenitor (Triticum turgidum L.). However, little is known about the physiological basis of this trait or about the relative contributions of allohexaploidization and subsequent evolutionary genetic changes on the trait development. Here, we compared the salt tolerance of a synthetic allohexaploid wheat (neo-6x) with its tetraploid (T. turgidum; BBAA) and diploid (Aegilops tauschii; DD) parents, as well as a natural hexaploid bread wheat (nat-6x). We studied 92 morphophysiological traits and analyzed homeologous gene expression of a major salt-tolerance gene High-Affinity K(+) Transporter 1;5 (HKT1;5). We observed that under salt stress, neo-6x exhibited higher fitness than both of its parental genotypes due to inheritance of favorable traits like higher germination rate from the 4x parent and the stronger root Na(+) retention capacity from the 2x parent. Moreover, expression of the D-subgenome HKT1;5 homeolog, which is responsible for Na(+) removal from the xylem vessels, showed an immediate transcriptional reprogramming following allohexaploidization, i.e., from constitutive high basal expression in Ae. tauschii (2x) to salt-induced expression in neo-6x. This phenomenon was also witnessed in the nat-6x. An integrated analysis of 92 traits showed that, under salt-stress conditions, neo-6x resembled more closely the 2x than the 4x parent, suggesting that the salt stress induces enhanced expressivity of the D-subgenome homeologs in the synthetic hexaploid wheat. Collectively, the results suggest that condition-dependent functionalization of the subgenomes might have contributed to the wide-ranging adaptability of natural hexaploid wheat.
Related JoVE Video
Self-assembled platinum nanoflowers on polydopamine-coated reduced graphene oxide for methanol oxidation and oxygen reduction reactions.
Chem Asian J
PUBLISHED: 07-26-2014
Show Abstract
Hide Abstract
The morphology- and size-controlled synthesis of branched Pt nanostructures on graphene is highly favorable for enhancing the electrocatalytic activity and stability of Pt. Herein, a facile approach is developed for the efficient synthesis of well-dispersed Pt nanoflowers (PtNFs) on the surface of polydopamine (PDA)-modified reduced graphene oxide (PDRGO), denoted as PtNFs/PDRGO, in high yield. The synthesis was performed by a simple heating treatment of an aqueous solution that contained K2 PtCl4 and PDA-modified graphene oxide (GO) without the need for any additional reducing agent, seed, surfactant, or organic solvent. The coated PDA serves not only as a reducing agent, but also as cross-linker to anchor and stabilize PtNFs on the PDRGO support. The as-prepared PtNFs/PDRGO hybrid, with spatially and locally separated PtNFs on PDRGO, exhibits superior electrocatalytic activity and stability toward both methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR) in alkaline solutions.
Related JoVE Video
Effects of cascaded vgb promoters on poly(hydroxybutyrate) (PHB) synthesis by recombinant Escherichia coli grown micro-aerobically.
Appl. Microbiol. Biotechnol.
PUBLISHED: 07-26-2014
Show Abstract
Hide Abstract
Micro-aeration is a situation that will be encountered in bacterial cell growth especially when the saturated dissolved oxygen level cannot match the demand from cells grown to a high density. Therefore, it is desirable to separate aerobic growth and micro-aerobic product formation into two stages using methods including anaerobic or micro-aerobic promoters that are inducible under low aeration intensity. Eleven potential low aeration-inducible promoters were cloned and studied for their induction strengths under micro-aerobic conditions. Of them, Vitreoscilla hemoglobin promoter (P vgb ) was found to be the strongest among all 11 promoters. At the same time, six E. coli hosts harboring poly(R-3-hydroxybutyrate) (PHB) synthesis operon phaCAB were compared for their ability to accumulate poly(hydroxyalkanoates) (PHA). E. coli S17-1 was demonstrated to be the best host achieving a 70 % (mass fraction) PHB in the cell dry weigh (CDW) after 48 h under micro-aerobic growth. Cascaded P vgb repeats (P nvgb ) were investigated for enhanced expression level under micro-aerobic growth. The highest PHA production was obtained when a promoter containing eight cascaded P vgb repeats (P 8vgb ) was used, 5.37 g/l CDW containing 90 % PHB was obtained from recombinant in E. coli S17-1. Cells grew further to 6.30 g/l CDW containing 91 % PHB when oxygen-responsive transcription factor ArcA (arcA) was deleted in the same recombinant E. coli S17-1. This study revealed that vgb promoter containing cascaded P vgb repeats (P 8vgb ) is useful for product formation under low aeration intensity.
Related JoVE Video
Size evolution of ion beam synthesized Pb nanoparticles in Al.
Nanoscale Res Lett
PUBLISHED: 07-10-2014
Show Abstract
Hide Abstract
The size evolution of Pb nanoparticles (NPs) synthesized by ion implantation in an epitaxial Al film has been experimentally investigated. The average radius R of Pb NPs was determined as a function of implantation fluence f. The R(f) data were analyzed using various growth models. Our observations suggest that the size evolution of Pb NPs is controlled by the diffusion-limited growth kinetics (R (2)?f). With increasing implantation current density, the diffusion coefficient of Pb atoms in Al is evident to be enhanced. By a comparative analysis of the R(f) data, values of the diffusion coefficient of Pb in Al were obtained.
Related JoVE Video
Two coupled effects of sub micron silica particles on the mechanical relaxation behavior of ethylene-propylene-diene rubber chains.
Soft Matter
PUBLISHED: 07-10-2014
Show Abstract
Hide Abstract
This article studied the influence of silica (SiO2) particles on the crosslinked network and the molecular mobility of ethylene-propylene-diene (EPDM) rubber chains by dynamic mechanical analysis (DMA). When SiO2 fraction is lower than 8 phr, the chain segments that participate in the glass-rubber transition (? transition) decrease with increasing the SiO2 content, while the whole crosslinked network is almost unaffected by the presence of SiO2. When the SiO2 fraction increases to about 20 phr, there appears a new tan?? peak (?' transition) above the ? transition. This could be because the crosslinking reaction took place only on a small scale and the formed network became gradually incomplete when the content of the particles exceeded some critical value, and the ?' transition is attributed primarily to the motion of non-elastic network chains loosely attached to the three-dimensional network. However, at SiO2 loadings higher than 40 phr, the crosslinking density was kept basically constant. The ?' transition is hindered by a restriction of the chain mobility due to SiO2. The different changes of ?' transition depended on the two coupled effects of SiO2, including restricting the chain mobility and decreasing the crosslinking density. Correspondingly, with increasing the mobility of EPDM chains and SiO2-induced strengthening, the mechanical properties of EPDM composite are dramatically improved. With the addition of 20 phr of SiO2 in the EPDM, a 113% increase in the elongation at break, a 510% increase in the fracture energy, and a 283% increase in the tensile strength are achieved.
Related JoVE Video
Roles of transforming growth factor-?1 and OB-cadherin in porcine cardiac valve myofibroblast differentiation.
FASEB J.
PUBLISHED: 07-09-2014
Show Abstract
Hide Abstract
Calcific aortic stenosis is a common disease, and some of its early causes are the activation and differentiation of resident fibroblasts to myofibroblasts in response to transforming growth factor ?1 (TGF-?1). The aim of this study was to understand how TGF-?1 and its downstream effector, OB-cadherin [cadherin 11 (CDH11)], regulate porcine myofibroblast phenotypes. Based on whole-genome microarrays, 95 and 107 genes are up- and down-regulated at both the early (8 h) and the late (24 h) time points of TGF-?1 treatment. Gene functions related to cell adhesion, skeletal system development, and extracellular matrix are up-regulated by TGF-?1, whereas oxidation-reduction and steroid metabolic process are down-regulated. Notably, one of the cell adhesion molecules, CDH11, is up-regulated by ?2-fold through both the Smad2/3 and the ERK pathways elicited by TGF-?1. CDH11 mediates cell-cell contacts in both valvular fibroblasts and myofibroblasts. Knockdown of CDH11 by small interfering RNA increases the myofibroblast phenotype, including an ?2-fold increase in ?-smooth muscle actin (?-SMA) expression and stress fiber formation. In contrast, increased binding of CDH11 through antibody treatment inhibits ?-SMA expression. This study presents gene functional changes in response to TGF-?1 at the systems level and supports an inhibitory role of CDH11 in myofibroblast differentiation.
Related JoVE Video
Boosting the photocurrent density of p-type solar cells based on organometal halide perovskite-sensitized mesoporous NiO photocathodes.
ACS Appl Mater Interfaces
PUBLISHED: 07-09-2014
Show Abstract
Hide Abstract
The p-n tandem design of a sensitized solar cell is a novel concept holding the potential to overcome the efficiency limitation of conventional single-junction sensitized solar cells. Significant improvement of the photocurrent density (Jsc) of the p-type half-cell is a prerequisite for the realization of a highly efficient p-n tandem cell in the future. This study has demonstrated effective photocathodes based on novel organometal halide perovskite-sensitized mesoporous NiO in liquid-electrolyte-based p-type solar cells. An acceptably high Jsc up to 9.47 mA cm(-2) and efficiency up to 0.71% have been achieved on the basis of the CH3NH3PbI3/NiO solar cell at 100 mW cm(-2) light intensity, which are significantly higher than those of any previously reported liquid-electrolyte-based p-type solar cells based on sensitizers of organic dyes or inorganic quantum dots. The dense blocking layer made by spray pyrolysis of nickel acetylacetonate holds the key to determining the current flow direction of the solar cells. High hole injection efficiency at the perovskite/NiO interface and high hole collection efficiency through the mesoporous NiO network have been proved by time-resolved photoluminescence and transient photocurrent/photovoltage decay measurements. The limitation of these p-type solar cells primarily rests with the adverse light absorption by the NiO mesoporous film; the secondary limitation arises from the highly viscous ethyl acetate-based electrolyte, which is helpful for the solar cell stability but hinders fluent diffusion into the pore channels, giving rise to a nonlinear dependence of Jsc on the light intensity.
Related JoVE Video
Malignant melanoma of the vagina: A case report and review of the literature.
Oncol Lett
PUBLISHED: 07-01-2014
Show Abstract
Hide Abstract
Primary malignant melanoma of the vagina is an extremely rare variant of melanoma that accounts for <3% of all vaginal malignancies. Primary malignant melanoma of the vagina has a worse prognosis as compared with non-genital melanomas or other vaginal malignant neoplasms. A-35-year-old female had a diagnosis of primary malignant melanoma of the vagina. A local excision of the tumor was first performed, followed by a radical excision as a further therapeutic measure. The patient returned after three weeks, presenting with a vesico-vaginal fistula. A conservative operation was subsequently performed in order to improve the quality of life of the patient. Pelvic metastases were identified 6 months after the completion of the last surgical therapy and subsequent follow-up examinations were performed in another hospital. The present case study describes the clinical features and surgical procedures of this patient with primary malignant melanoma of the vagina. In conclusion, melanoma of the vagina is an extremely aggressive cancer and the overall prognosis is poor despite the various treatment options.
Related JoVE Video
Entrapment of alkaloids within silver: from enantioselective hydrogenation to chiral recognition.
Chem. Commun. (Camb.)
PUBLISHED: 06-28-2014
Show Abstract
Hide Abstract
An alkaloid@Ag composite was prepared for the first time and used as a cathode for the enantioselective hydrogenation. Excellent yield and a remarkable enantiomeric excess value were obtained under mild conditions. Moreover, alkaloid@Ag after extraction was demonstrated to retain some chirality by linear sweep voltammetry.
Related JoVE Video
Destruction of DDIT3/CHOP protein by wild-type SPOP but not prostate cancer-associated mutants.
Hum. Mutat.
PUBLISHED: 06-27-2014
Show Abstract
Hide Abstract
Characterization of the exome and genome of prostate cancers by next-generation sequencing has identified numerous genetic alternations. SPOP (speckle-type POZ protein) was identified as one of the most frequently affected genes by somatic point mutations in prostate cancer, suggesting SPOP is potentially a key driver for prostate cancer development and progression. However, how SPOP mutations contribute to prostate cancer remains to be elucidated. SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex and selectively recruits substrates for their ubiquitination and subsequent degradation. DDIT3 is an endoplasmic reticulum (ER) stress-responsive transcription factor playing an essential role in apoptotic execution pathways triggered by ER stress. Here, we identified DDIT3/CHOP as a bona fide substrate for the SPOP-CUL3-RBX1 E3 ubiquitin ligase complex. SPOP recognizes a Ser/Thr-rich degron in the transactivation domain of DDIT3 and triggers DDIT3 degradation via the ubiquitin-proteasome pathway. Strikingly, prostate cancer-associated mutants of SPOP are defective in promoting DDIT3 degradation. This study reveals novel molecular events underlying the regulation of DDIT3 protein homeostasis and provides insight in understanding the relationship between SPOP mutations and ER stress dysregulation in prostate cancer.
Related JoVE Video
Endoplasmic reticulum stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) protects against pressure overload-induced heart failure and lung remodeling.
Hypertension
PUBLISHED: 06-23-2014
Show Abstract
Hide Abstract
Studies have reported that development of congestive heart failure is associated with increased endoplasmic reticulum stress. Double stranded RNA-activated protein kinase R-like endoplasmic reticulum kinase (PERK) is a major transducer of the endoplasmic reticulum stress response and directly phosphorylates eukaryotic initiation factor 2?, resulting in translational attenuation. However, the physiological effect of PERK on congestive heart failure development is unknown. To study the effect of PERK on ventricular structure and function, we generated inducible cardiac-specific PERK knockout mice. Under unstressed conditions, cardiac PERK knockout had no effect on left ventricular mass, or its ratio to body weight, cardiomyocyte size, fibrosis, or left ventricular function. However, in response to chronic transverse aortic constriction, PERK knockout mice exhibited decreased ejection fraction, increased left ventricular fibrosis, enhanced cardiomyocyte apoptosis, and exacerbated lung remodeling in comparison with wild-type mice. PERK knockout also dramatically attenuated cardiac sarcoplasmic reticulum Ca(2+)-ATPase expression in response to aortic constriction. Our findings suggest that PERK is required to protect the heart from pressure overload-induced congestive heart failure.
Related JoVE Video
Identification and characterization of gastrointestinal hormone immunoreactive cells in the skin and parotoids of Chinese toad Bufo gargarizans.
Folia Histochem. Cytobiol.
PUBLISHED: 06-22-2014
Show Abstract
Hide Abstract
The skin and skin secretion of Chinese toad Bufo gargarizans have long been used in traditional Chinese medicine. However, the exact types and location of bioactive substances in Bufo gargarizans skin still have not been fully elucidated. The aim of the study was to investigate the distribution and density of six types of gastrointestinal (GI) hormone immunoreactive (IR) cells in the skin and parotoids of Bufo gargarizans. Immunohistochemistry was used for qualitative and semiquantitative analysis of GI hormone presence in the dorsal and ventral skin, and parotoids of eight adult Chinese toads. Six types of IR cells were found: serotonin (5-HT), glucagon (GLU), gastrin (GAS), somatostatin (SS), pancreatic polypeptide (PP) and neuropeptide Y(NPY) IR cells. They were mainly present in the epidermis and skin glands. 5-HT-IR cells were distributed in all layers of epidermis and glands, with higher density in the glands. Glucagon was prominently expressed in the epidermis and the bottle-shaped glands of parotoids; however, it was not present in the granular glands of skin and parotoids. The distributions of GAS and SS-IR cells were similar since they were present mainly in mucous, granular and bottle-shaped glands, while these cell types were absent in the differentiated glands of parotoids. PP-IR cells were predominant in the granular glands and the bottle-shaped glands. The expression of NPY was high in epidermal stratum granulosum and mucous glands of the dorsal skin, the bottle-shaped glands and differentiated glands of parotoids, while NPY-IR was rarely seen in the granular glands of ventral skin, and not present in the granular glands of dorsal skin and parotoids. The expression of several types of GI hormones in the skin and parotoids of Bufo gargarizans varies depending on tissue and type of glands.
Related JoVE Video
Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells.
Oncol. Rep.
PUBLISHED: 06-16-2014
Show Abstract
Hide Abstract
Available evidence on the proliferation-promoting effect of HE4 remains controversial, and few studies have been carried out on the molecular mechanism of chemoresistance mediated by HE4. The aim of the present study was to investigate the influence of exogenous recombinant HE4 protein on proliferation and resistance to carboplatin in ovarian cancer cells. The human ovarian cancer cell line (SKOV-3) was exposed to recombinant HE4 protein (0-1 µg/ml) for different durations based on the schemes. Cell viability was evaluated by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Markers of apoptosis (Bax and Bcl-2) were assessed by western blotting. Furthermore, Affymetrix microarray analysis was performed to investigate transcriptome profiling. The differential expression of four genes was verified by quantitative real-time PCR. The HE4 protein enhanced cell viability, promoted accumulation of cells in the G2/M phase and attenuated carboplatin-induced apoptosis. HE4 markedly decreased the Bax/Bcl-2 ratio. Candidate genes (387) (236 upregulated and 151 downregulated) were obtained by microarray analysis. Among those upregulated, several Gene Ontology (GO) terms related to cell cycle regulation and proliferation were significantly overrepresented and those within the downregulated dataset included genes involved in several aspects of the DNA damage response such as positive regulation of apoptosis. No information concerning the EGFR-MAPK pathways in a recent report on HE4 was acquired. The mRNA expression of the candidate genes determined by quantitative real-time PCR was significantly correlated with the microarray data. The present study indicates that the HE4 protein plays a promotive role in the proliferation and resistance to carboplatin in ovarian cancer cells, implicating the value of HE4 to predict tumor growth potential and resistance to platinum-based chemotherapy in epithelial ovarian cancer (EOC).
Related JoVE Video
CYR61 overexpression associated with the development and poor prognosis of ovarian carcinoma.
Med. Oncol.
PUBLISHED: 06-10-2014
Show Abstract
Hide Abstract
Cysteine-rich 61 (CYR61) has been proven to be an oncogene with potential predictive and prognostic implications in a variety of human cancers. However, the expression pattern of CYR61 and its role in ovarian carcinoma remains largely unknown. In this study, the mRNA and protein levels of CYR61 in normal ovaries and ovarian carcinoma tissues were evaluated using reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blotting. Compared to normal ovarian tissues, the mRNA and protein levels of CYR61 were significantly higher in ovarian carcinoma tissues. Moreover, receiver operating characteristic (ROC) curve analysis, Spearman's rank correlation, Kaplan-Meier plots, and the Cox proportional hazards regression model were used to investigate the potential association of the CYR61 protein with the development of ovarian carcinoma in an ovarian carcinoma cohort. Based on ROC curve analysis, high expression of CYR61 was defined as a tumor in which more than 70 % of cells were positively stained. Based on this cutoff value, high expression of CYR61 was detected in 51.5 % of invasive carcinomas, 35.3 % of borderline tumors, 25.9 % of cystadenomas, and 20 % in the normal ovaries. In ovarian carcinomas, CYR61 overexpression was associated with advanced FIGO stage. Univariate survival analysis on the ovarian carcinoma cohorts showed that overexpression of CYR61 was associated with poor survival of ovarian cancer patients. Multivariate analysis suggested that the protein level of CYR61 was an independent and significant prognostic factor for ovarian carcinoma. Our results suggest that the CYR61 protein is an important and independent biomarker for prognostic implications of ovarian carcinoma.
Related JoVE Video
Exploring the potential of self-assembled mixed micelles in enhancing the stability and oral bioavailability of an acid-labile drug.
Eur J Pharm Sci
PUBLISHED: 05-09-2014
Show Abstract
Hide Abstract
Oral delivery of many drugs is plagued with limited solubility and/or poor stability. This paper aimed to explore the performance of polymeric mixed micelles on solubilization, stabilization and bioavailability enhancement with stiripentol as model drug. Stiripentol-loaded mixed micelles were prepared by solvent-diffusion method: rapid dispersion of an ethanol solution containing stiripentol, monomethoxy poly(ethylene glycol)-b-poly(?-caprolactone) and sodium oleate into water. Stiripentol micelles were characterized by the particle size, entrapment efficiency, in vitro drug release, TEM, DSC and FTIR. The pharmacokinetic profile of stiripentol was determined in rats after oral administration of stiripentol micelles. The obtained stiripentol micelles were 44.2 nm in size with an entrapment efficiency over 90%. It was shown that micelles substantially improved the solubility and gastric stability of stiripentol. The oral absorption of stiripentol was also enhanced to a great extent with a relative bioavailability of 157% and 444% to the commercial formulation (Diacomit®) and in-house suspensions. Mixed micelles assembled by di-block copolymer/sodium oleate exhibited a good potential in the improvement of drug stability and bioavailability. It should be a promising carrier for oral delivery of therapeuticals with solubility and stability issues.
Related JoVE Video
Overexpression of RFC3 is correlated with ovarian tumor development and poor prognosis.
Tumour Biol.
PUBLISHED: 04-21-2014
Show Abstract
Hide Abstract
Replication factor C3 (RFC3) is an oncogene that can potentially predict prognosis in a variety of human cancers. RFC3 expression in ovarian carcinoma has not yet been determined. In this study, we evaluated the messenger RNA (mRNA) and protein expression levels of RFC3 in normal ovarian and ovarian carcinoma tissues using reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blots (WB). Results showed that higher RFC3 mRNA and protein levels were detected in ovarian carcinoma tissues by RT-PCR and WB. High RFC3 expression was defined as positive staining in >70 % of each tumor cell. High RFC3 expression was detected in 28.1, 17.6, 11.1, and 5.0 % of invasive carcinomas, borderline tumors, cystadenomas, and in normal ovary cells, respectively. Overexpression of RFC3 was associated with later pN status (p?=?0.001), pM status (p?=?0.001), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (p?=?0.012) in ovarian carcinomas. Univariate survival analyses showed that RFC3 overexpression was also associated with shortened patient survival (mean 7.7 months in tumors with RFC3 overexpression vs 92.9 months in tumors with normal RFC3 levels; p?
Related JoVE Video
Isothermal and rapid detection of pathogenic microorganisms using a nano-rolling circle amplification-surface plasmon resonance biosensor.
Biosens Bioelectron
PUBLISHED: 04-21-2014
Show Abstract
Hide Abstract
Rolling circle amplification (RCA) of DNA is a sensitive and cost effective method for the rapid identification of pathogens without the need for sequencing. In this study, a surface plasmon resonance DNA biosensor based on RCA with a gold (Au) nanoparticle surface was established for isothermal identification of DNA. The probes included a specific padlock probe, a capture probe (CP), which is bound to biotin, and an Au nanoparticle-modified probe, which hybridizes with the RCA products. The CP was assembled on gold nanoparticles to increase its ability to bind and hybridize. The linear padlock probe, which was designed to circularize by ligation upon recognition of the bacterial pathogen-specific sequence in 16S rDNA, hybridizes to fully complementary sequences within the CP. Upon recognition, each target gene DNA is distinguished by localization onto the corresponding channel on the chip surface. Then, the immobilized CPs act as primers to begin the in situ solid-phase RCA reaction, which produces long single-stranded DNA. The RCA products fixed on the chip surface cause significant surface plasmon resonance angle changes. We demonstrated that six different bacterial pathogens can be identified simultaneously and that 0.5 pM of synthetic oligonucleotides and 0.5 pg ?l(-1) of genomic DNA from clinical samples can be detected by this method with low background signals. Therefore, the multiplex diagnostic method provides a highly sensitive and specific approach for the rapid identification of positive samples.
Related JoVE Video
Endoplasmic reticulum stress-induced hepatic stellate cell apoptosis through calcium-mediated JNK/P38 MAPK and Calpain/Caspase-12 pathways.
Mol. Cell. Biochem.
PUBLISHED: 04-18-2014
Show Abstract
Hide Abstract
Recent reports considered that it was the disturbance of calcium homeostasis and the accumulation of misfolded proteins in the endoplasmic reticulum (ER) that activated hepatic stellate cells (HSCs) apoptosis and promoted fibrosis resolution. However, the signal-transducing events that are activated by ER stress after HSCs activation were incompletely understood. In this study, we induced ER stress with thapsigargin (TG), and determined the activation of calpain and the cleavage of caspase by analyzing the protein levels and the correspondingly increased intracellular calcium levels and the induction of the proapoptotic transcription factor CHOP. Moreover, the phosphorylation of JNK and p38 MAPK were followed by the activation of the executioner caspases, caspase-3. As expected, preventing an increase in intracellular calcium levels using intracellular calcium chelators, EGTA, and BAPTA/AM, could substantially inhibit the phosphorylation of JNK and p38 MAPK, abolish the activation of calpains, namely caspase-12, caspase-9, and caspase-3, and provide significant protection for TG-treated activated HSCs. Interestingly, pretreatment with p38 MAPK inhibitor SB202190, JNK inhibitor SP600125, the pan-caspase inhibitor z-VAD-FMK, or calpain inhibitors calpeptin, significantly reduced the cell apoptosis and the cleavage of caspase-12 and caspase-3. However, pretreatment with z-VAD-FMK failed to reduce the activation of calpain. Additionally, pretreatment with SB202190 and SP600125 also decreased the expression of CHOP. Importantly, PDGF-induced collagen Col1?1 and ?-smooth muscle actin (?-SMA), markers for the perpetuation phase of HSCs activation, were inhibited in TG-treated activated HSCs. These findings showed that the Calpain/Caspase-12 activation induced by ER stress and the JNK/p38 MAPK phosphorylation induced by the increase of intracellular calcium concentration releasing from ER are the novel signaling pathway underlying the molecular mechanism of fibrosis recovery.
Related JoVE Video
Neurenteric cyst of the area postrema.
Case Rep Neurol Med
PUBLISHED: 03-22-2014
Show Abstract
Hide Abstract
Neurenteric cysts are CNS lesions most frequently occurring in the spinal cord. Intracranial neurenteric cysts are rarer, typically presenting with headache, mass effect, or location-specific symptoms. The area postrema is known as the emetic center of the brain; lesions can cause nausea and vomiting. Our case, featuring a neurenteric cyst of the area postrema, illustrates the importance of considering a neurological etiology for nonspecific symptoms that otherwise elude explanation. Our patient presented with acute decompensated hydrocephalus upon exploratory abdominal laparoscopy for unresolving abdominal pain. The patient had an eight-month history of unexplained intermittent nausea, vomiting, and abdominal pain. These bouts increased in frequency during the weeks before acute presentation, prompting exploratory abdominal laparoscopy. The acute decompensation was managed by ventriculostomy, and cranial MRI revealed a cystic mass by the floor of the fourth ventricle. After the patient stabilized and returned to neurological baseline, suboccipital craniectomy and resection were performed. The mass was histologically identified as a neurenteric cyst. The patient was free from neurological complaints at one-year follow-up, indicating that the successful resection of the area postrema-associated neurenteric cyst resolved her previous symptoms. Thus, some intracranial lesions can masquerade as nonspecific symptoms, presenting a challenge to accurate diagnosis.
Related JoVE Video
The presence of tumor-infiltrating IL-17-producing cells in juvenile nasopharyngeal angiofibroma tumor microenvironment is a poor prognostic factor.
Am J Otolaryngol
PUBLISHED: 03-12-2014
Show Abstract
Hide Abstract
Although juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor histologically, it demonstrates aggressive propensity of locally destructive growth causing bone erosion. The patients with JNA remain high recurrence rate after surgical excision. Th17 cells secrete the proinflammatory cytokine interleukin-17 (IL-17), and play an important role in carcinogenesis and tumor progression. So far, no studies have focused on the significance of IL-17-producing cells in the JNA tumor microenvironment. The current study was designed to investigate the localization and level of tumor-infiltrating IL-17-producing cells in JNA microenvironment. The presence and number of IL-17-producing cells were further analyzed for a possible association with clinicopathological features and disease outcome.
Related JoVE Video
Pyrolysis technologies for municipal solid waste: A review.
Waste Manag
PUBLISHED: 02-23-2014
Show Abstract
Hide Abstract
Pyrolysis has been examined as an attractive alternative to incineration for municipal solid waste (MSW) disposal that allows energy and resource recovery; however, it has seldom been applied independently with the output of pyrolysis products as end products. This review addresses the state-of-the-art of MSW pyrolysis in regards to its technologies and reactors, products and environmental impacts. In this review, first, the influence of important operating parameters such as final temperature, heating rate (HR) and residence time in the reaction zone on the pyrolysis behaviours and products is reviewed; then the pyrolysis technologies and reactors adopted in literatures and scale-up plants are evaluated. Third, the yields and main properties of the pyrolytic products from individual MSW components, refuse-derived fuel (RDF) made from MSW, and MSW are summarised. In the fourth section, in addition to emissions from pyrolysis processes, such as HCl, SO2 and NH3, contaminants in the products, including PCDD/F and heavy metals, are also reviewed, and available measures for improving the environmental impacts of pyrolysis are surveyed. It can be concluded that the single pyrolysis process is an effective waste-to-energy convertor but is not a guaranteed clean solution for MSW disposal. Based on this information, the prospects of applying pyrolysis technologies to dealing with MSW are evaluated and suggested.
Related JoVE Video
Different efficacy of EGFR tyrosine kinase inhibitors and prognosis in patients with subtypes of EGFR-mutated advanced non-small cell lung cancer: a meta-analysis.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 02-16-2014
Show Abstract
Hide Abstract
Nearly 85 % of lung-cancer-specific epidermal growth factor receptor (EGFR) sensitive mutations comprise a substitution at position 858 (21L858R) and deletion mutants in exon 19 (19del). The aim of this study was to assess the role of EGFR mutation subtypes in predicting the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) and the prognosis of patients with advanced non-small cell lung cancer (NSCLC).
Related JoVE Video
Piperlongumine induces apoptosis and synergizes with cisplatin or paclitaxel in human ovarian cancer cells.
Oxid Med Cell Longev
PUBLISHED: 02-14-2014
Show Abstract
Hide Abstract
Piperlongumine (PL), a natural alkaloid from Piper longum L., possesses the highly selective and effective anticancer property. However, the effect of PL on ovarian cancer cells is still unknown. In this study, we firstly demonstrate that PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore, PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the intracellular reactive oxidative species (ROS) in a dose- and time-dependent manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth effect on human ovarian cancer cells. Collectively, our study provides new therapeutic potential of PL on human ovarian cancer.
Related JoVE Video
Prognostic value of matrix metalloproteinase 9 expression in patients with juvenile nasopharyngeal angiofibroma: tissue microarray analysis.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 02-13-2014
Show Abstract
Hide Abstract
Although JNA is a benign neoplasm histopathologically, it has a propensity for locally destructive growth and remains a higher postoperative recurrence rate. The aim of this study was to analyze the expression and localization of MMP-9 in JNA using tissue microarray to elucidate its correlation with clinicopathological features and recurrence.
Related JoVE Video
Downregulation of leaf flavin content induces early flowering and photoperiod gene expression in Arabidopsis.
BMC Plant Biol.
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
Riboflavin is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), essential cofactors for many metabolic enzymes that catalyze a variety of biochemical reactions. Previously we showed that free flavin (riboflavin, FMN, and FAD) concentrations were decreased in leaves of transgenic Arabidopsis plants expressing a turtle riboflavin-binding protein (RfBP). Here, we report that flavin downregulation by RfBP induces the early flowering phenotype and enhances expression of floral promoting photoperiod genes.
Related JoVE Video
Distribution of endocrine cells in the digestive tract of Alligator sinensis during the active and hibernating period.
Tissue Cell
PUBLISHED: 01-19-2014
Show Abstract
Hide Abstract
The digestive tract is the largest endocrine organ in the body; the distribution pattern of endocrine cells varies with different pathological and physiological states. The aim of the present study was to investigate the distributed density of 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SS) and vasoactive intestinal peptide (VIP) immunoreactive (IR) cells in the digestive tract of Alligator sinensis during the active and hibernating period by immunohistochemical (IHC) method. The results indicated that 5-HT-IR cells were distributed throughout the entire digestive tract, which were most predominant in duodenum and jejunum. The density increased significantly in stomach and duodenum during hibernation. GAS-IR cells were limited in small stomach and small intestine. The density decreased significantly in small stomach during hibernation, while increased in duodenum. What's more, most of the endocrine cells in duodenum were generally spindle shaped with long cytoplasmic processes ending in the lumen during hibernation. SS-IR cells were limited in stomach and small stomach. The density increased in stomach while decreased in small stomach during hibernation, meanwhile, fewer IR cells occurred in small intestine. VIP-IR cells occurred in stomach and small stomach. The density decreased in small stomach, while increased in stomach during hibernation. These results indicated that the endocrine cells in different parts of digestive tract varied differently during hibernation, their changes were adaptive response to the hibernation.
Related JoVE Video
CdS urchin-like microspheres/?-Fe?O? and CdS/Fe?O? nanoparticles heterostructures with improved photocatalytic recycled activities.
J Colloid Interface Sci
PUBLISHED: 01-19-2014
Show Abstract
Hide Abstract
The heterostructures of three-dimensional CdS urchin-like microspheres separately decorated with hematite ?-Fe2O3 or magnetite Fe3O4 nanoparticles were successfully synthesized via a two-step solvothermal deposition. Each CdS urchin-like microspheres had an average diameter of 2 ?m, which was composed of nanorods with average diameters of 10nm. ?-Fe2O3 and Fe3O4 nanoparticles, with diameters of about 20 nm and 30 nm, respectively, anchored on the nanorods of CdS urchins. The photoluminescence behaviors of CdS urchins were conserved in both CdS/?-Fe2O3 and CdS/Fe3O4 heteronanostructures, and CdS/Fe3O4 heteronanostructure displayed ferromagnetic properties of the Fe3O4 nanoparticles, which makes it easily magnetically separated from the dispersion after photocatalysis and hence reused. Furthermore, the CdS/?-Fe2O3 heteronanostructure exhibited superior photocatalytic performances under visible light irradiation over pure CdS urchins and both the heteronanostructures showed improved photocatalytic recycled activities.
Related JoVE Video
Endoplasmic reticulum stress is the crossroads of autophagy, inflammation, and apoptosis signaling pathways and participates in liver fibrosis.
Inflamm. Res.
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
The objective of the review is to examine the crossroads of autophagy, inflammation, and apoptosis signaling pathways and their participation in liver fibrosis.
Related JoVE Video
Effects of valproic Acid on axonal regeneration and recovery of motor function after peripheral nerve injury in the rat.
Arch Bone Jt Surg
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
Valproic acid (VPA) is used to be an effective anti-epileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal regulated kinase pathway, and increases bcl-2 and growth cone-associated protein 43 levels in spinal cord. In the present research we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function following sciatic nerve transaction in rats.
Related JoVE Video
Regional principal color based saliency detection.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Saliency detection is widely used in many visual applications like image segmentation, object recognition and classification. In this paper, we will introduce a new method to detect salient objects in natural images. The approach is based on a regional principal color contrast modal, which incorporates low-level and medium-level visual cues. The method allows a simple computation of color features and two categories of spatial relationships to a saliency map, achieving higher F-measure rates. At the same time, we present an interpolation approach to evaluate resulting curves, and analyze parameters selection. Our method enables the effective computation of arbitrary resolution images. Experimental results on a saliency database show that our approach produces high quality saliency maps and performs favorably against ten saliency detection algorithms.
Related JoVE Video
Determination of production regions for pollution-free Chinese medicinal materials by geographic information system: Achyranthes bidentata (Niu Qi) in Tianjin as an example.
Chin Med
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The land and ecology suitability for producing pollution-free Chinese medicinal materials should be evaluated based on Geographic Information System (GIS). This study aims to determine production regions for pollution-free Achyranthes bidentata in Tianjin as a case to illustrate the workflow based on GIS.
Related JoVE Video
Brain temperature and its fundamental properties: a review for clinical neuroscientists.
Front Neurosci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Brain temperature, as an independent therapeutic target variable, has received increasingly intense clinical attention. To date, brain hypothermia represents the most potent neuroprotectant in laboratory studies. Although the impact of brain temperature is prevalent in a number of common human diseases including: head trauma, stroke, multiple sclerosis, epilepsy, mood disorders, headaches, and neurodegenerative disorders, it is evident and well recognized that the therapeutic application of induced hypothermia is limited to a few highly selected clinical conditions such as cardiac arrest and hypoxic ischemic neonatal encephalopathy. Efforts to understand the fundamental aspects of brain temperature regulation are therefore critical for the development of safe, effective, and pragmatic clinical treatments for patients with brain injuries. Although centrally-mediated mechanisms to maintain a stable body temperature are relatively well established, very little is clinically known about brain temperature's spatial and temporal distribution, its physiological and pathological fluctuations, and the mechanism underlying brain thermal homeostasis. The human brain, a metabolically "expensive" organ with intense heat production, is sensitive to fluctuations in temperature with regards to its functional activity and energy efficiency. In this review, we discuss several critical aspects concerning the fundamental properties of brain temperature from a clinical perspective.
Related JoVE Video
HIF-1? signaling activation by post-ischemia treatment with astragaloside IV attenuates myocardial ischemia-reperfusion injury.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
In this study, we evaluated the effect of astragaloside IV (Ast IV) post-ischemia treatment on myocardial ischemia-reperfusion (IR) injury (IRI). We also examined whether hypoxia inducible factor-1? (HIF-1?) and its downstream gene-inducible nitric oxide (NO) synthase (iNOS) play roles in the cardioprotective effect of Ast IV. Cultured cardiomyocytes and perfused isolated rat hearts were exposed to Ast IV during reperfusion in the presence or absence of the HIF-1? inhibitor 2-methoxyestradiol (2-MeOE2). The post-ischemia treatment with Ast IV protected cardiomyocytes from the apoptosis and death induced by simulated IRI (SIRI). Additionally, in cardiomyocytes, 2-MeOE2 and HIF-1? siRNA treatment each not only abolished the anti-apoptotic effect of post-ischemia treatment with Ast IV but also reversed the upregulation of HIF-1? and iNOS expression. Furthermore, after treatment with Ast IV, post-ischemic cardiac functional recovery and lactate dehydrogenase (LDH) release in the coronary flow (CF) were improved, and the myocardial infarct size was decreased. Moreover, the number of apoptotic cells was reduced, and the upregulation of the anti-apoptotic protein Bcl2 and downregulation of the pro-apoptotic protein Caspase3 were reversed. 2-MeOE2 reversed these effects of Ast IV on IR-injured hearts. These results suggest that post-ischemia treatment with Ast IV can attenuate IRI by upregulating HIF-1? expression, which transmits a survival signal to the myocardium.
Related JoVE Video
A novel role of CDX1 in embryonic epicardial development.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The molecular mechanism that regulates epicardial development has yet to be understood. In this study, we explored the function of CDX1, a Caudal-related family member, in epicardial epithelial-to-mesenchymal transition (EMT) and in the migration and the differentiation of epicardium-derived progenitors into vascular smooth muscle cells. We detected a transient expression of CDX1 in murine embryonic hearts at 11.5 days post coitum (dpc). Using a doxycycline-inducible CDX1 mouse model, primary epicardium, and ex vivo heart culture, we further demonstrated that ectopic expression of CDX1 promoted epicardial EMT. In addition, a low-dose CDX1 induction led to enhanced migration and differentiation of epicardium-derived cells into ?-SMA+ vascular smooth muscles. In contrast, either continued high-level induction of CDX1 or CDX1 deficiency attenuated the ability of epicardium-derived cells to migrate and to mature into smooth muscles induced by TGF-?1. Further RNA-seq analyses showed that CDX1 induction altered the transcript levels of genes involved in neuronal development, angiogenesis, and cell adhesions required for EMT. Our data have revealed a previously undefined role of CDX1 during epicardial development, and suggest that transient expression of CDX1 promotes epicardial EMT, whereas subsequent down-regulation of CDX1 after 11.5 dpc in mice is necessary for further subepicardial invasion of EPDCs and contribution to coronary vascular endothelium or smooth muscle cells.
Related JoVE Video
The Glycosyltransferase Involved in Thurandacin Biosynthesis Catalyzes Both O- and S-Glycosylation.
J. Am. Chem. Soc.
PUBLISHED: 12-16-2013
Show Abstract
Hide Abstract
The S-glycosyltransferase SunS is a recently discovered enzyme that selectively catalyzes the conjugation of carbohydrates to the cysteine thiol of proteins. This study reports the discovery of a second S-glycosyltransferase, ThuS, and shows that ThuS catalyzes both S-glycosylation of the thiol of cysteine and O-glycosylation of the hydroxyl group of serine in peptide substrates. ThuS-catalyzed S-glycosylation is more efficient than O-glycosylation, and the enzyme demonstrates high tolerance with respect to both nucleotide sugars and peptide substrates. The biosynthesis of the putative products of the thuS gene cluster was reconstituted in vitro, and the resulting S-glycosylated peptides thurandacin A and B exhibit highly selective antimicrobial activity toward Bacillus thuringiensis.
Related JoVE Video
Leukemia cells induce changes in human bone marrow stromal cells.
J Transl Med
PUBLISHED: 11-25-2013
Show Abstract
Hide Abstract
Bone marrow stromal cells (BMSCs) are multipotent cells that support angiogenesis, wound healing, and immunomodulation. In the hematopoietic niche, they nurture hematopoietic cells, leukemia, tumors and metastasis. BMSCs secrete of a wide range of cytokines, growth factors and matrix proteins which contribute to the pro-tumorigenic marrow microenvironment. The inflammatory cytokines IFN-? and TNF-? change the BMSC secretome and we hypothesized that factors produced by tumors or leukemia would also affect the BMSC secretome and investigated the interaction of leukemia cells with BMSCs.
Related JoVE Video
Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K/AKT pathway.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-11-2013
Show Abstract
Hide Abstract
Matrix elasticity regulates proliferation, apoptosis, and differentiation of many cell types across various tissues. In particular, stiffened matrix in fibrotic lesions has been shown to promote pathogenic myofibroblast activation. To better understand the underlying pathways by which fibroblasts mechano-sense matrix elasticity, we cultured primary valvular interstitial cells (VICs) isolated from porcine aortic valves on poly(ethylene glycol)-based hydrogels with physiologically relevant and tunable elasticities. We show that soft hydrogels preserve the quiescent fibroblast phenotype of VICs much better than stiff plastic plates. We demonstrate that the PI3K/AKT pathway is significantly up-regulated when VICs are cultured on stiff gels or tissue culture polystyrene compared with freshly isolated VICs. In contrast, myofibroblasts de-activate and pAKT/AKT decreases as early as 2 h after reducing the substrate modulus. When PI3K or AKT is inhibited on stiff substrates, myofibroblast activation is blocked. When constitutively active PI3K is overexpressed, the myofibroblast phenotype is promoted even on soft substrates. These data suggest that valvular fibroblasts are sensing the changes in matrix elasticity through the PI3K/AKT pathway. This mechanism may be used by other mechano-sensitive cells in response to substrate modulus, and this pathway may be a worthwhile target for treating matrix stiffness-associated diseases. Furthermore, hydrogels can be designed to recapitulate important mechanical cues in native tissues to preserve aspects of the native phenotype of primary cells for understanding basic cellular responses to biophysical and biochemical signals, and for tissue-engineering applications.
Related JoVE Video
Functional evaluation in the rat sciatic nerve defect model: a comparison of the sciatic functional index, ankle angles, and isometric tetanic force.
Plast. Reconstr. Surg.
PUBLISHED: 10-30-2013
Show Abstract
Hide Abstract
The sciatic functional index has long been the standard method of assessing motor recovery in the rat sciatic nerve model. The relative subjective nature of the assessment has led to development of newer methods, including video gait analysis and quantitative measurement of isometric tetanic muscle force.
Related JoVE Video
Loss of the eukaryotic initiation factor 2? kinase general control nonderepressible 2 protects mice from pressure overload-induced congestive heart failure without affecting ventricular hypertrophy.
Hypertension
PUBLISHED: 10-28-2013
Show Abstract
Hide Abstract
In response to several stresses, including nutrient deprivation, general control nonderepressible 2 kinase (GCN2) attenuates mRNA translation by phosphorylating eukaryotic initiation factor 2?(Ser51). Energy starvation is known to exacerbate congestive heart failure, and eukaryotic initiation factor 2?(Ser51) phosphorylation is increased in the failing heart. However, the effect of GCN2 during the evolution of congestive heart failure has not been tested. In this study, we examined the influence of GCN2 expression in response to a cardiac stress by inducing chronic pressure overload with transverse aortic constriction in wild-type and GCN2 knockout mice. Under basal conditions, GCN2 knockout mice had normal left ventricular structure and function, but after transverse aortic constriction, they demonstrated less contractile dysfunction, less increase in lung weight, less increase in lung inflammation and vascular remodeling, and less myocardial apoptosis and fibrosis compared with wild-type mice, despite an equivalent degree of left ventricular hypertrophy. As expected, GCN2 knockout attenuated transverse aortic constriction-induced cardiac eukaryotic initiation factor 2?(Ser51) phosphorylation and preserved sarcoplasmic reticulum Ca(2+) ATPase expression compared with wild-type mice. Interestingly, the expression of the antiapoptotic protein Bcl-2 was significantly elevated in GCN2 knockout hearts, whereas in isolated neonatal cardiomyocytes, selective knockdown of GCN2 increased Bcl-2 protein expression and enhanced myocyte resistance to an apoptotic stress. Collectively, our data support the notion that GCN2 impairs the ventricular adaptation to chronic pressure overload by reducing Bcl-2 expression and increasing cardiomyocyte susceptibility to apoptotic stimuli. Our findings suggest that strategies to reduce GCN2 activity in cardiac tissue may be a novel approach to attenuate congestive heart failure development.
Related JoVE Video
The role of tissue factor pathway inhibitor-2 in malignant transformation of sinonasal inverted papilloma.
Eur Arch Otorhinolaryngol
PUBLISHED: 10-27-2013
Show Abstract
Hide Abstract
The aim was to evaluate the potential role of tissue factor pathway inhibitor-2 (TFPI-2) in the process of malignant transformation of sinonasal inverted papilloma (SIP). We evaluated the expression of TFPI-2 in 23 SIP and 8 SIP with squamous cell carcinoma (IPcSCC), compared to 9 normal sinonasal mucosa by means of Western blot and immunohistochemistry staining. In addition, angiogenesis, vascular endothelial growth factor (VEGF) expression and microvessel density marked by CD105 staining were assessed. Correlation of TFPI-2 expression and angiogenesis in the process of malignant transformation of SIP was investigated. Western blot results demonstrated that the protein level of TFPI-2 in IPcSCC was significantly lower than that in the control group (P < 0.01). In addition, significant difference in TFPI-2 protein expression between SIP and IPcSCC was detected (P < 0.01). Higher number of microvessel per unit area (MVNA) was observed in IPcSCC compared to SIP (P < 0.01). Correlational analysis indicated positive correlation of VEGF and MVNA (r = 0.735), inverse correlation of TFPI-2 and MVNA (r = -0.318). However, no significant correlation between TFPI-2 and VEGF was detected. We conclude that TFPI-2 might be a regulatory molecule in the malignant potential of SIP. Down regulation of TFPI-2 is associated with increased MVNA in IPcSCC, which may be involved in the process of malignant transformation of SIP.
Related JoVE Video
Desiccation and cold storage of Galleria?mellonella cadavers and effects on in?vivo production of Steinernema carpocapsae.
Pest Manag. Sci.
PUBLISHED: 10-24-2013
Show Abstract
Hide Abstract
Direct application of insect cadavers infected with entomopathogenic nematodes (EPN) can successfully control target pest insects. Little is known about the effects of environmental factors (desiccation and temperature) on the production process for infective juveniles (IJ) in insects.
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.