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Find video protocols related to scientific articles indexed in Pubmed.
Chemical Bonding in a Linear Chromium Metal String Complex.
Inorg Chem
PUBLISHED: 11-11-2014
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A combined experimental and theoretical electron density study of the shortest trichromium metal wire, Cr3(dpa)4Cl2·(C2H5OC2H5)x(CH2Cl2)1-x (1, dpa = bis(2-pyridyl)amido), is reported. High resolution X-ray diffraction data has been collected both at 100 K using a conventional X-ray source (DS1) and at 15 K using a synchrotron X-ray source (DS2). The linear chromium string is terminated by Cl(-) ions at both ends, and each Cr atom is also coordinated by four N atoms from bridging dpa ligands. The two Cr-Cr bond distances are unequal at 100 K (with d(Cr1-Cr2) being 0.029 Å shorter than d(Cr2-Cr3)) but at 15 K they are almost equal (0.002 Å difference). Analysis of the slightly elongated thermal ellipsoids of the Cr2 atom suggests that it is not due to disorder, but the presence of a shallow potential energy surface. Laplacian maps clearly show local valence shell charge concentration (VSCC) in the electron density along the bisector of the equatorial Cr-N bonds. Integration over the atomic basins indicates that Cr2 has smaller atomic charge and volume than Cr1 and Cr3. The topological characterization of the Cr-Cr bonds indicates partly covalent characters with electron density at the bond critical point of ?0.3 e Å(-3) and negative total energy density. The delocalization index of Cr-Cr is 0.8 for Cr1-Cr2 and 0.08 for Cr1-Cr3. Second-order perturbation analysis shows high stabilization energy of the Cr-Cr bonds (E(2) ? 190 kcal mol(-1)). Delocalization indices and source function and natural bond orbital analyses are all indicative of localized Cr-Cr bonding interactions.
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The progression of muscle fatigue during exercise estimation with the aid of high-frequency component parameters derived from ensemble empirical mode decomposition.
IEEE J Biomed Health Inform
PUBLISHED: 09-06-2014
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Muscle fatigue is often monitored via the median frequency derived from the surface electromyography (sEMG) power spectrum during isometric contractions. The power spectrum of sEMG shifting toward lower frequencies can be used to quantify the electromanifestation of muscle fatigue. The dynamic sEMG belongs to a nonstationary signal, which will be affected by the electrode moving, the shift of the muscle, and the change of innervation zone. The goal of this study is to find a more sensitive and stable method in order to sense the progression of muscle fatigue in the local muscle during exercise in healthy people. Five male and five female volunteers participated. Each subject was asked to run on a multifunctional pedaled elliptical trainer for about 30 min, twice a week, and was recorded a total of six times. Three decomposed methods, discrete wavelet transform (DWT), empirical mode decomposition (EMD), and ensemble EMD (EEMD), were used to sense the progression of muscle fatigue. They compared with each other. Although the highest frequency components of sEMG by DWT, EMD, and EEMD have the better performance to sense the progression of muscle fatigue than the raw sEMG, the EEMD has the best performance to reduce nonstationary characteristics and noise of the dynamic sEMG.
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Effect of uraemic status on immunofluorescence and enzyme-linked immunosorbent assays for detection of human herpesvirus type 8 antibodies.
Pathology
PUBLISHED: 08-28-2014
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Our previous study showed that human herpesvirus type 8 (HHV-8) seroprevalence was significantly higher in patients with end-stage renal disease (ESRD) immediately after haemodialysis than in healthy controls based on an immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA). However, other studies indicated that ESRD patients and healthy controls had similar HHV-8 seroprevalence. This study aimed to investigate whether this discrepancy is due to the effect of uraemic status.Plasma samples from 162 ESRD patients, taken immediately before and after haemodialysis, and 162 age and sex matched healthy controls were analysed for HHV-8 antibodies using both IFA and ELISA.HHV-8 seropositivities based on IFA and ELISA, both before and after haemodialysis, were significantly greater in ESRD patients than in healthy controls (p?
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Pin1 positively affects tumorigenesis of esophageal squamous cell carcinoma and correlates with poor survival of patients.
J. Biomed. Sci.
PUBLISHED: 08-27-2014
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Pin1 promotes oncogenesis by regulating multiple oncogenic signaling. In this study, we investigated the involvement of Pin1 in tumor progression and in the prognosis of human esophageal squamous cell carcinoma (ESCC).
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Clinical applications of the indirect immunofluorescence assay for detection of anti-cell membrane-associated DNA antibodies in Juvenile Systemic Lupus Erythematosus.
Pediatr. Res.
PUBLISHED: 08-15-2014
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BackgroundJuvenile-onset systemic lupus erythematosus (JSLE) has a higher mortality risk compared to adult-onset SLE. We compared the diagnostic value of anti-cmDNA antibodies with that of anti-nucleosome antibodies (AnuA), anti-Sm antibodies and anti-dsDNA antibodies and human B lymphocyte Raji cells with that of human promyelocytic leukemia HL60 cells as substrates in an indirect immunofluorescence assay to detect anti-cmDNA antibodies in JSLE patients.MethodsWe recruited 92 JSLE patients and 71 patients with other rheumatic diseases. Anti-cmDNA antibodies and ANA were detected in patient sera using indirect immunofluorescence assays. Anti-dsDNA antibodies were detected by combining ELISA and indirect immunofluorescence. Anti-Sm antibodies were detected by double immunodiffusion assay and immunoblotting, while anti-nucleosome antibodies (AnuA) were detected by ELISA.ResultsJSLE group had a significantly higher percentage of patients positive for anti-cmDNA compared to patients with other rheumatoid diseases. Using one antibody for diagnosis, anti-cm DNA antibodies has highest accuracy as 84.0%, using 2 antibodies, the combination of anti-cm DNA and anti-dsDNA antibodies has 90.8 % accuracy. Raji cells used as substrate demonstrated a stronger intensity of fluorescent patterns compared to HL60 cells.ConclusionThe high sensitivity, specificity and accuracy of detection of anti-cmDNA antibodies make it a valuable diagnostic tool for JSLE.Pediatric Research (2014); doi:10.1038/pr.2014.182.
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High seroprevalence of human herpesvirus type 8 infection in males with advanced lung carcinoma.
Med. Microbiol. Immunol.
PUBLISHED: 08-15-2014
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Human herpesvirus type 8 (HHV-8) DNA is consistently found in all types of Kaposi's sarcoma, which is prevalent in immunocompromised patients. Patients with advanced lung carcinoma often showed immunologic abnormalities, and prevalence of HHV-8 infection is unclear. In this study, blood samples from 109 lung carcinoma patients and 109 age- and sex-matched healthy controls were analyzed for lymphocyte and monocyte counts, and for antibody, DNA, and genotype of HHV-8. Lung carcinoma patients had significantly lower lymphocyte and higher monocyte counts than healthy controls (p < 0.0001, both). HHV-8 seropositivity was more prevalent in lung carcinoma patients (41.3 %), particularly in male patients (50.8 %), than in controls (24.8 %) (p = 0.01 and 0.002, respectively). The seropositivity was also significantly higher in male (50.8 %) than female patients (27.3 %, p = 0.01). Titers of HHV-8 antibody in patients also significantly exceeded those in controls (p = 0.004). Under a higher threshold (antibody titer ?1:160) which is equivalent to that of enzyme-linked immunosorbent assay, lung carcinoma patients still had higher HHV-8 seropositivity than controls (p = 0.006). Three patients with stage IV lung carcinoma were positive for HHV-8 DNA with K1 gene subtype C3, D1, and E, respectively; they had much lower lymphocyte counts (658 ± 132 µL) than patients positive for HHV-8 antibodies only (1,449 ± 873 µL). The study indicates that lung carcinoma patients, particularly males, have a high seroprevalence of HHV-8. HHV-8 DNA detected in the patients with advanced lung carcinoma may be a result of virus reactivation in the immunocompromised status.
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[Effect of the anterior aspect of sacral nerve root tunnel on iliosacral screw placement on the standard lateral image of sacrum].
Zhongguo Gu Shang
PUBLISHED: 07-18-2014
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To introduce the location and course of S1, S2 sacral nerve root tunnel and to clarify the significance of the anterior aspect of sacral nerve root tunnel on placement of iliosacral screw on the standard lateral sacral view.
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The epigenetic factor Kmt2a/Mll1 regulates neural progenitor proliferation and neuronal and glial differentiation.
Dev Neurobiol
PUBLISHED: 06-05-2014
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Multiple epigenetic factors play a critical role in cell proliferation and differentiation. However, their function in embryogenesis, especially in neural development, is currently unclear. The Trithorax group (TrxG) homolog KMT2A (MLL1) is an important epigenetic regulator during development and has an especially well-defined role in hematopoiesis. Translocation and aberrant expression of KMT2A is often observed in many tumors, indicating its proto-oncogenic character. Here, we show that Kmt2a was essential for neural development in zebrafish embryos. Disrupting the expression of Kmt2a using morpholino antisense oligonucleotides and a dominant-negative variant resulted in neurogenic phenotypes, including downregulated proliferation of neural progenitors, premature differentiation of neurons, and impaired gliogenesis. This study therefore revealed a novel function of Kmt2a in cell proliferation and differentiation, providing further insight into the function of TrxG proteins in neural development and brain tumors. © 2014 Wiley Periodicals, Inc. Develop Neurobiol, 2014.
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The R-curve behavior and thermal shock resistance for Al2O3 + ZrO2 laminated nanoceramics.
J Nanosci Nanotechnol
PUBLISHED: 04-17-2014
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The properties of thermal shock resistances of Al2O3 + ZrO2 monolayer and laminated ceramics are determined by the indentation method. The relationships between the R-curve, the thermal shock resistance properties and the mechanism of strengthening and toughening are also studied in this paper. The Al2O3 + ZrO2 laminated ceramics have an R-curve feature and a decrease in the sensitivity of the strength to the size of surface cracks. Indentation thermal shock test shows that the critical temperature difference of the Al2O3 + ZrO2 laminated ceramics is 400 degrees C, 150 degrees C higher than that of the monolayer ceramics. Under the condition of the surface compressive stress, the surface fracture appearance is more uneven and the fracture mechanism is different along the interface. The R-curve and thermal shock resistance properties are improved by strengthening the transformation effect resulting from the surface compressive stress.
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A preclinical evaluation of a novel multikinase inhibitor, SKLB-329, as a therapeutic agent against hepatocellular carcinoma.
Int. J. Cancer
PUBLISHED: 04-16-2014
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Hepatocellular carcinoma (HCC) is a serious life-threatening malignant disease of liver. Molecular targeted therapies are considered a promising strategy for the treatment of HCC. Sorafenib is the first, and so far the only targeted drug approved by the US Food and Drug Administration (FDA) for clinical therapy of HCC. Despite being effective in some HCC patients, some demerits of sorafenib in the treatment of HCC, such as modest survival benefits, and drug resistance, have also been reported, which highlights the unmet medical need among patients with HCC. Here, we report a novel multikinase inhibitor discovered by us, SKLB-329, which potently inhibits angiogenesis-related kinases including VEGFR1/2/3, and FGFR2, and the Src kinase. SKLB-329 significantly inhibited endothelial cell growth, migration, invasion and tube formation. It showed potent anti-angiogenic activity in a transgenic zebrafish model. Moreover, SKLB-329 could efficiently restrain the proliferation of HCC cells through down-regulation of Src-mediated FAK and Stat3 activity. In vivo, oral administration of SKLB-329 considerably suppressed the tumor growth in HCC xenograft models (HepG2 and SMMC7721) in a dose-dependent manner. In all of the in vitro and in vivo assays of this investigation, sorafenib was used as a positive control, and in most assays SKLB-329 exhibited a higher potency compared with the positive control. In addition, SKLB-329 also bears favorable pharmacokinetic properties. Collectively, the results of preclinical studies presented here demonstrate that SKLB-329 is a promising drug candidate for HCC treatment.
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Assessment of the potential of polyphenols as a CYP17 inhibitor free of adverse corticosteroid elevation.
Biochem. Pharmacol.
PUBLISHED: 04-07-2014
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Inhibition of 17?-hydroxylase/17,20-lyase (CYP17), which dictates the proceeding of androgen biosynthesis, is recommended as an effective treatment for androgen-dependent diseases. However, androgen depletion by selective CYP17 inhibition is accompanied with corticosteroid elevation, which increases risk of cardiovascular diseases. In this study, we evaluated the likelihood of polyphenols as a CYP17 inhibitor without cardiovascular complications. All examined polyphenols significantly inhibited CYP17 in human adrenocortical H295R cells, but their effects on androgen and cortisol biosynthesis were diverse. Resveratrol was the most potent CYP17 inhibitor with an approximate IC50 of 4 ?M, and the inhibition might weigh on the 17?-hydroxylase activity more than the 17,20-lyase activity. Resveratrol also inhibited 21?-hydroxylase (CYP21) essential for corticosteroid biosynthesis but to a lesser extent, thus preventing the occurrence of cortisol elevation following CYP17 blockade. Although transcriptional down-regulation was important for ?-naphthoflavone-mediated CYP17 inhibition, resveratrol inhibited CYP17 and CYP21 mainly at the level of enzyme activity rather than enzyme abundance and cytochrome P450 electron transfer. Daidzein also inhibited CYP17 and CYP21 although less potent than resveratrol. Daidzein was the only polyphenol showing inhibition of 3?-hydroxysteroid dehydrogenase type II (3?HSD2). The exceptional 3?HSD2 inhibition led to dehydroepiandrosterone accumulation alongside daidzein-caused androgen biosynthetic impairment. In contrast, androgen and cortisol secretion was increased or remained normal under ?-naphthoflavone and ?-naphthoflavone treatments, suggesting that CYP17 inhibition was counteracted by increased substrate generation. ?-naphthoflavone and ?-naphthoflavone also enhanced the formation of cortisol from 17-hydroxyprogesterone and testosterone from androstenedione. Our findings suggest a potential application of resveratrol in androgen deprivation therapy.
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Sinoatrial node electrical activity modulates pulmonary vein arrhythmogenesis.
Int. J. Cardiol.
PUBLISHED: 02-18-2014
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Sinoatrial node (SAN) dysfunction increases the occurrences of atrial fibrillation (AF). The pulmonary veins (PVs) play a critical role in the pathophysiology of AF. The purpose of this study was to evaluate whether SAN electrical activity can modulate PV arrhythmogenesis.
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A monounsaturated fatty acid (oleic acid) modulates electrical activity in atrial myocytes with calcium and sodium dysregulation.
Int. J. Cardiol.
PUBLISHED: 01-28-2014
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Obesity and metabolic syndrome are important risk factors for atrial fibrillation. High plasma concentrations of monounsaturated fatty acids, including oleic acid (OLA), are frequently noted in obese individuals and patients with metabolic syndrome. However, it is not clear whether monounsaturated fatty acids (MUFAs) can directly modulate the electrophysiological characteristics of atrial myocytes.
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Semi-automatic segmentation and classification of Pap smear cells.
IEEE J Biomed Health Inform
PUBLISHED: 01-10-2014
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Cytologic screening has been widely used for detecting the cervical cancers. In this study, a semiautomatic PC-based cellular image analysis system was developed for segmenting nuclear and cytoplasmic contours and for computing morphometric and textual features to train support vector machine (SVM) classifiers to classify four different types of cells and to discriminate dysplastic from normal cells. A software program incorporating function, including image reviewing and standardized denomination of file names, was also designed to facilitate and standardize the workflow of cell analyses. Two experiments were conducted to verify the classification performance. The cross-validation results of the first experiment showed that average accuracies of 97.16% and 98.83%, respectively, for differentiating four different types of cells and in discriminating dysplastic from normal cells have been achieved using salient features (8 for four-cluster and 7 for two-cluster classifiers) selected with SVM recursive feature addition. In the second experiment, 70% (837) of the cell images were used for training and 30% (361) for testing, achieving an accuracy of 96.12% and 98.61% for four-cluster and two-cluster classifiers, respectively. The proposed system provides a feasible and effective tool in evaluating cytologic specimens.
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Undifferentiated carcinoma of the pituitary gland: A case report and review of the literature.
Oncol Lett
PUBLISHED: 01-03-2014
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Primary pituitary gland cancer is extremely rare. The current study presents the case of a patient diagnosed with pituitary cancer three months after completing surgery and post-operative chemoradiotherapy for hypopharyngeal cancer. In this report we discuss 57-year-old patient who presented with diplopia and ptosis four months following the completion of treatment for hypopharyngeal cancer. A poorly-differentiated pituitary carcinoma was located. Despite aggressive treatment and surgical excision with postoperative chemoradiotherapy, the disease progressed rapidly and the patient succumbed due to multiple metastases and organ failure. This case report indicates a possible correlation between irradiation and the development of pituitary cancer.
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[Thyroid lymphography:a new clinical approach for protecting parathyroid in surgery].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 12-17-2013
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To research the role of lymph tracers to protect parathyroid in surgery for papillary thyroid carcinoma.
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Courtship Patterns in the Drosophila montium Species Subgroup: Repeated Loss of Precopulatory Courtship?
Zool. Sci.
PUBLISHED: 12-11-2013
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During precopulatory courtship, male Drosophila typically produce wing vibration to generate species-specific songs before mounting females. Three species in the lini clade of the montium species subgroup have been found to produce species-specific sine song only after mounting and during copulation. Here we investigated and analyzed the courtship behavior of 29 species in the montium subgroup from video and song recordings and measured the duration of wing vibration. We describe a great diversity of courtship behavior in the montium subgroup. The courtship patterns can be categorized into four types in the montium subgroup: 1) type P/C, species with both precopulatory and copulatory courtship, such as D. parvula and D. nikananu, 2) type P-/C, species with sporadic precopulatory and mainly copulatory courtship, such as D. auraria and D. triauraria. 3) type C, species with only copulatory courtship, such as D. tani and D. pectinifera, 4) type C-, species with only very brief copulatory courtship, such as D. rufa and D. asahinai. According to a phylogenetic tree based on sequences of mitochondrial COI and COII, and the nuclear Adh, both precopulatory courtship and copulatory courtship were present in the most basal species D. parvula. Each of two branches in the montium subgroup contains four types of courtship behavior. Type C is present in each sub-branch. These results suggest that the courtship behavior initially involved both precopulatory and copulatory courtship, but that subsequently precopulatory courtship has gradually been lost in the montium subgroup. We suggest reasons why precopulatory behavior might come to be lost in the montium subgroup.
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[A prospective randomized and controlled study on no drainage after surgery for benign thyroid disorders].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 11-08-2013
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To evaluate the necessity of drainage after thyroidectomy for benign thyroid disorders.
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Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells.
Oncol. Rep.
PUBLISHED: 10-15-2013
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Survivin is overexpressed in transitional cell carcinoma (TCC), the most common type of bladder cancer. Previous reports demonstrated that knockdown of survivin by siRNA induced apoptosis of TCC cells. The present study evaluated the therapeutic effects of sepantronium bromide (YM155), a novel small molecule survivin inhibitor under clinical trials, on TCC cells in vitro. BFTC905, a grade III TCC cell line derived from a patient of blackfoot disease in Taiwan, was the most gemcitabine-resistant cell line when compared to BFTC909, TSGH8301 and T24 in cytotoxicity assay, resulting from upregulation of securin and bcl-2 after gemcitabine treatment. YM155 caused potent concentration?dependent cytotoxicity in 4 TCC cell lines (IC50s ?20 nM), but exhibited no cytotoxicity in survivin-null primary human urothelial cells. For BFTC905 cells, addition of gemcitabine and/or cisplatin, the standard TCC chemotherapy regimen, to YM155 did not exert additive cytotoxic effects. Molecular analyses indicated that YM155 inhibited the proliferation of BFTC905 cells by increasing p27kip1, suppressing Ki-67, and inducing quiescence. In addition, YM155 elicited apoptosis manifested with DNA fragmentation through suppressing the expression of survivin, securin and bcl-2. Furthermore, YM155 induced autophagy in BFTC905 cells as autophagic inhibitor, 3-methyladenine, attenuated YM155-induced LC3B-II levels and reversed the cytotoxicity of YM155. mTOR inhibitors sirolimus and everolimus did not increase YM155-induced expression of LC3B-II nor augment YM155-induced cytotoxicity. These results indicate that YM155 exerts its lethal effect on BFTC905 cells via apoptotic and autophagic death pathways and suggest that YM155 may be a potential drug for the therapy of gemcitabine-resistant bladder cancer.
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Exercise muscle fatigue detection system implementation via wireless surface electromyography and empirical mode decomposition.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Surface electromyography (sEMG) is an important measurement for monitoring exercise and fitness. A wireless Bluetooth transmission sEMG measurement system with a sampling frequency of 2 KHz is developed. Traditional muscle fatigue is detected from the median frequency of the sEMG power spectrum. The regression slope of the linear regression of median frequency is an important muscle fatigue index. As fatigue increases, the power spectrum of the sEMG shifts toward lower frequencies. The goal of this study is to evaluate the sensitivity of empirical mode decomposition (EMD) quantifying the electrical manifestations of the local muscle fatigue during exercising in health people. We also compared this method with the raw data and discrete wavelet transform (DWT). Five male and five female volunteers participated. Each subject was asked to run on a multifunctional pedaled elliptical trainer for about 30 minutes, twice a week, and there were a total of six recording times for each subject with a wireless EMG recording system. The results show that sensitivity of the highest frequency component of EMD is better than the highest frequency component of DWT, and raw data.
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Etv5a regulates the proliferation of ventral mesoderm cells and the formation of hemato-vascular derivatives.
J. Cell. Sci.
PUBLISHED: 10-07-2013
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Hematopoietic and vascular endothelial cells constitute the circulatory system and are both generated from the ventral mesoderm. However, the molecules and signaling pathways involved in ventral mesoderm formation and specification remain unclear. We found that zebrafish etv5a was expressed in the ventral mesoderm during gastrulation. Knockdown of Etv5a using morpholinos increased the proliferation of ventral mesoderm cells and caused defects in hematopoietic derivatives and in vascular formation. By contrast, the formation of other mesodermal derivatives, such as pronephros, somites and the gut wall, was not affected. Knockdown specificity was further confirmed by overexpression of an etv5a construct lacking its acidic domain. In conclusion, our data reveal that etv5a is essential for the inhibition of ventral mesoderm cell proliferation and for the formation of the hemato-vascular lineage.
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Rosiglitazone promotes neurite outgrowth and mitochondrial function in N2A cells via PPARgamma pathway.
Mitochondrion
PUBLISHED: 09-20-2013
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Several pieces of evidence indicate that peroxisome proliferator-activated receptor gamma (PPAR?) stimulation promotes neuronal differentiation. However, to date, the effects of a synthetic PPAR? agonist (Rosiglitazone, Rosi) on neurite outgrowth have not yet been well described. Here we have evaluated the effects of Rosi on neurite outgrowth and mitochondrial function in the mouse neuroblastoma Neuro 2a (N2A) cell line. Our results show that Rosi promotes neurite outgrowth of N2A cells and significantly increases the population of neurite-bearing cells, with apparent increase of intracellular calcium and the expression of calmodulin-dependent kinase I (CaMKI). Rosi also increases the intracellular cAMP and expression of both protein kinase A (PKA) and cAMP response element binding protein (CREB). Phosphorylation of CREB was also detected in the Rosi treated N2A cells. Moreover, Rosi significantly increases the transcription of AMP-activated kinase (AMPK) and Sirtuin 1 (SIRT1). Besides, the expression of PPAR coactivator 1? (PGC1?), as well as the mRNA level its downstream genes, including nuclear respiratory factors 1 and 2 (NRF1 and NRF2) and mitochondrial transcription factor A (Tfam) were induced by Rosi treatments. Furthermore, Rosi increases the level of ATP, D-loop, and mitochondrial mass in N2A cells. Collectively, these findings provide an array of evidence that PPAR? activation provides beneficial neuronal networks within neurite outgrowth.
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Improvement of optical transmittance and electrical properties for the Si quantum dot-embedded ZnO thin film.
Nanoscale Res Lett
PUBLISHED: 09-04-2013
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A Si quantum dot (QD)-embedded ZnO thin film is successfully fabricated on a p-type Si substrate using a ZnO/Si multilayer structure. Its optical transmittance is largely improved when increasing the annealing temperature, owing to the phase transformation from amorphous to nanocrystalline Si QDs embedded in the ZnO matrix. The sample annealed at 700[degree sign]C exhibits not only high optical transmittance in the long-wavelength range but also better electrical properties including low resistivity, small turn-on voltage, and high rectification ratio. By using ZnO as the QDs matrix, the carrier transport is dominated by the multistep tunneling mechanism, the same as in a n-ZnO/p-Si heterojunction diode, which clearly differs from that using the traditional matrix materials. Hence, the carriers transport mainly in the ZnO matrix, not through the Si QDs. The unusual transport mechanism using ZnO as matrix promises the great potential for optoelectronic devices integrating Si QDs.
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Intracranial papillary meningioma: a clinicopathologic study of 30 cases at a single institution.
Neurosurgery
PUBLISHED: 08-08-2013
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Papillary meningioma (PM) is an uncommon meningioma subtype, and the clinical characteristics remain unclear.
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Knockdown of cyclin-dependent kinase 10 (cdk10) gene impairs neural progenitor survival via modulation of raf1a gene expression.
J. Biol. Chem.
PUBLISHED: 07-31-2013
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In this study, we used zebrafish as an animal model to elucidate the developmental function of cdk10 in vertebrates. In situ hybridization analyses demonstrated that cdk10 is expressed throughout development with a relative enrichment in the brain in the late stages. Similar to its mammalian ortholog, cdk10 can interact with the transcription factor ETS2 and exhibit kinase activity by phosphorylating histone H1. Morpholino-based loss of cdk10 expression caused apoptosis in sox2-positive cells and decreased the expression of subsequent neuronal markers. Acetylated tubulin staining revealed a significant reduction in the number of Rohon-Beard sensory neurons in cdk10 morphants. This result is similar to that demonstrated by decreased islet2 expression in the dorsal regions. Moreover, cdk10 morphants exhibited a marked loss of huC-positive neurons in the telencephalon and throughout the spinal cord axis. The population of retinal ganglion cells was also diminished in cdk10 morphants. These phenotypes were rescued by co-injection of cdk10 mRNA. Interestingly, the knockdown of cdk10 significantly elevated raf1a mRNA expression. Meanwhile, an MEK inhibitor (U0126) recovered sox2 and ngn1 transcript levels in cdk10 morphants. Our findings provide the first functional characterization of cdk10 in vertebrate development and reveal its critical function in neurogenesis by modulation of raf1a expression.
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Facile synthesis of heterotrimetallic metal-string complex [NiCoRh(dpa)4Cl2] through direct metal replacement.
Chem. Commun. (Camb.)
PUBLISHED: 07-30-2013
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This communication provides a practical strategy for the synthesis of heterotrimetallic extended metal atom chains with supported dpa(-) ligands. The transformation of the CoCoRh to a NiCoRh trinuclear complex can be achieved by direct metallic replacement. Furthermore, the first (CoRh)(4+) metal-metal bond is described here.
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Dioxin and Estrogen Signaling in Lung Adenocarcinoma Cells with Different Aryl Hydrocarbon Receptor/Estrogen Receptor ? Phenotypes.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 07-17-2013
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Evidence suggests that estrogen affects the pulmonary response to carcinogenic pollutants, such as dioxins. In this study, we examined dioxin and estrogen signaling cross-talk in lung adenocarcinoma cell lines that were engineered to exhibit different aryl hydrocarbon receptor (AhR)/estrogen receptor (ER) ? phenotypes. Data showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) weakly antagonized estrogen-activated ER? activity in cells expressing abundant ER?, but little AhR. Increase of AhR expression or presence of a dioxin-responsive element in proximity silenced the antiestrogenic effect of TCDD. AhR was bound to dioxin-responsive element and transcriptionally active in both TCDD-untreated and -treated lung adenocarcinoma cells. 17?-estradiol (E2) reduced basal and TCDD-induced AhR activity only in ER?-positive cells. AhR and ER? exhibited a protein-protein interaction in the presence of E2. Cotreatment with TCDD moderated this protein interaction. Colocalization of ER? and AhR at the estrogen-responsive site under E2 and TCDD/E2 treatments implied that E2???ER? might hijack AhR away from the dioxin-responsive site. Increasing the relative expression of AhR to ER? counteracted inhibition of AhR activity by E2???ER?. When AhR and ER? were both highly expressed, TCDD and E2 up-regulated expression of dual-responsive genes cytochrome P450 (CYP) 1A1 and CYP1B1 in a cumulative manner, increasing the danger of metabolic activation of carcinogens. Whereas TCDD???AhR and E2???ER? appeared to regulate CYP1B1 separately through their binding sites, E2???ER? increased the TCDD responsiveness and mRNA expression of CYP1A1 in a noncanonical way. In conclusion, AhR/ER? expression pattern, estrogen level, and promoter context determine the genomic action of dioxin in lung adenocarcinoma cells.
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High expression of CHRNA1 is associated with reduced survival in early stage lung adenocarcinoma after complete resection.
Ann. Surg. Oncol.
PUBLISHED: 06-18-2013
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Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths around the world, and a high recurrence rate after complete resection is an important issue reducing the cure rate and survival of patients with early stage NSCLC. Several pathologic biomarkers are associated with recurrence in early stage lung cancer after complete resection.
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Loss of RUNX3 increases osteopontin expression and promotes cell migration in gastric cancer.
Carcinogenesis
PUBLISHED: 06-17-2013
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Loss of RUNX3 expression is frequently observed in gastric cancer and is highly associated with lymph node metastasis and poor prognosis. However, the underlying molecular mechanisms of gastric cancer remain unknown. In this study, we found that the protein levels of RUNX3 and osteopontin (OPN) are inversely correlated in gastric cancer clinical specimens and cell lines. Furthermore, similar inverse trends between RUNX3 and OPN messenger RNA (mRNA) expression were demonstrated in six out of seven normal-tumor-paired gastric cancer clinical specimens. In addition, low RUNX3 and high OPN expression were associated with poor prognosis in gastric cancer patients. Ectopic expression of green fluorescent protein-RUNX3 reduced OPN protein and mRNA expression in the AGS and SCM-1 gastric cancer cell lines. In contrast, knockdown of RUNX3 in GES-1, a normal gastric epithelial cell line, increased OPN expression. Although three RUNX3-binding sequences have been identified in the OPN promoter region, direct binding of RUNX3 to the specific binding site, -142 to -137bp, was demonstrated by chromatin immunoprecipitation assay. The binding of RUNX3 to the OPN promoter significantly decreased OPN promoter activity. The knockdown of OPN or overexpression of RUNX3 inhibited cell migration in AGS and SCM-1 cells; however, the coexpression of RUNX3 and OPN reversed the RUNX3-reduced migration ability in AGS and SCM-1 cells. In contrast, the knockdown of both RUNX3 and OPN inhibited RUNX3-knockdown-induced migration of GES-1 cells. Together, our data demonstrated that RUNX3 is a transcriptional repressor of OPN and that loss of RUNX3 upregulates OPN, which promotes migration in gastric cancer cells.
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Fast fabrication of self-ordered anodic porous alumina on oriented aluminum grains by high acid concentration and high temperature anodization.
Nanotechnology
PUBLISHED: 04-25-2013
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Anodic porous alumina, which exhibits a characteristic nanohoneycomb structure, has been used in a wide range of nanotechnology applications. The conventional fabrication method of mild anodization (MA) requires a prolonged anodization time which is impractical for batch processing, and self-ordered porous structures can only be formed within narrow processing windows so that the dimensions of the resultant structures are extremely limited. The alternative hard anodization (HA) may easily result in macroscopic defects on the alumina surface. In this work, by systematically varying the anodization conditions including the substrate grain orientation, electrolyte concentration, temperature, voltage, and time, a new oxalic acid based anodization method, called high acid concentration and high temperature anodization (HHA), is found, which can result in far better self-ordering of the porous structures at rates 7-26 times faster than MA, under a continuous voltage range of 30-60 V on (001) oriented Al grains. Unlike HA, no macroscopic defects appear under the optimum self-ordered conditions of HHA at 40 V, even for pore channels grown up to high aspect ratios of more than 3000. Compared to MA and HA, HHA provides more choices of self-ordered nano-porous structures with fast and mechanically stable formation features for practical applications.
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Proteomic analysis of the cerebrospinal fluid of Parkinsons disease patients pre- and post-deep brain stimulation.
Cell. Physiol. Biochem.
PUBLISHED: 04-17-2013
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To investigate alterations in protein expression associated with deep brain stimulation (DBS) in an attempt to elucidate possible mechanisms of action .
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Nonsurgical management of mitral valve endocarditis due to Cardiobacterium valvarum in a patient with a ventricular septal defect.
J. Clin. Microbiol.
PUBLISHED: 04-10-2013
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Cardiobacterium valvarum is a relatively novel agent of infective endocarditis. We describe the first case of infective endocarditis due to this pathogen in the Asian Pacific. This case is unique in its involvement of the mitral valve as well as its clinical resolution exclusively resulting from treatment with antibiotics without resorting to valve replacement/explantation.
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High seroprevalence of human herpesvirus type 8 in patients with end-stage renal disease in Taiwan.
J. Clin. Virol.
PUBLISHED: 03-14-2013
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Human herpesvirus type 8 (HHV-8) is the aetiologic agent of Kaposis sarcoma (KS). The incidence of KS in renal transplant patients is much higher than in healthy controls. The risk is even higher among recipients seropositive for HHV-8 before transplantation. Patients with end-stage renal disease (ESRD) are immunocompromised and are candidates for renal transplantation, but HHV-8 seroprevalence in ESRD patients has not been well documented.
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The critical role of protein arginine methyltransferase prmt8 in zebrafish embryonic and neural development is non-redundant with its paralogue prmt1.
PLoS ONE
PUBLISHED: 03-12-2013
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Protein arginine methyltransferase (PRMT) 1 is the most conserved and widely distributed PRMT in eukaryotes. PRMT8 is a vertebrate-restricted paralogue of PRMT1 with an extra N-terminal sequence and brain-specific expression. We use zebrafish (Danio rerio) as a vertebrate model to study PRMT8 function and putative redundancy with PRMT1. The transcripts of zebrafish prmt8 were specifically expressed in adult zebrafish brain and ubiquitously expressed from zygotic to early segmentation stage before the neuronal development. Whole-mount in situ hybridization revealed ubiquitous prmt8 expression pattern during early embryonic stages, similar to that of prmt1. Knockdown of prmt8 with antisense morpholino oligonucleotide phenocopied prmt1-knockdown, with convergence/extension defects at gastrulation. Other abnormalities observed later include short body axis, curled tails, small and malformed brain and eyes. Catalytically inactive prmt8 failed to complement the morphants, indicating the importance of methyltransferase activity. Full-length prmt8 but not prmt1 cRNA can rescue the phenotypic changes. Nevertheless, cRNA encoding Prmt1 fused with the N-terminus of Prmt8 can rescue the prmt8 morphants. In contrast, N-terminus- deleted but not full-length prmt8 cRNA can rescue the prmt1 morphants as efficiently as prmt1 cRNA. Abnormal brain morphologies illustrated with brain markers and loss of fluorescent neurons in a transgenic fish upon prmt8 knockdown confirm the critical roles of prmt8 in neural development. In summery, our study is the first report showing the expression and function of prmt8 in early zebrafish embryogenesis. Our results indicate that prmt8 may play important roles non-overlapping with prmt1 in embryonic and neural development depending on its specific N-terminus.
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PEDF promotes self-renewal of limbal stem cell and accelerates corneal epithelial wound healing.
Stem Cells
PUBLISHED: 03-06-2013
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Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF) increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ?Np63?, Bmi-1, and ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was capable of increasing the numbers of ?Np63?-positive cells. The mitogenic effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78-121) was as effective as the full length PEDF in LSC expansion in suspension culture and limbal equivalent formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound healing. Microscopically, 44-mer PEDF advanced the early proliferative response in limbus, increased the proliferation of ?Np63?-positive cells both in limbus and in epithelial healing front, and assisted the repopulation of limbus in the late phase of wound healing. In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of PEDF and its fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound.
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PKC mediates fluctuant ERK-paxillin signaling for hepatocyte growth factor-induced migration of hepatoma cell HepG2.
Cell. Signal.
PUBLISHED: 02-28-2013
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Hepatocyte growth factor (HGF) is critical for triggering metastasis of hepatocellular carcinoma cell (HCC). Extracellular signal-regulated kinase (ERK) mediates HGF-induced cell migration via focal adhesion signaling. Protein kinase C (PKC) is a negative regulator of ERK activation, however, both PKC and ERK were required for HGF-induced cell migration. To address this intriguing issue, the signal mechanisms for HGF-induced HepG2 cell migration were investigated in a long-term fashion. HGF-induced phosphorylations of ERK, Src (at Tyr 416) and paxillin (at Ser178 and Tyr31) were up and down for 3 times within 24h. HGF also induced fluctuant PKC activation and Rac degradation. Consistently, HGF induced intermittent actin polarization within 24h, which can be blocked by the inhibitors of PKC (Bisindolymaleimide) and ERK. Inhibitor studies revealed that ERK was required for HGF-induced paxillin phosphorylation at Ser178, whereas PKC and Rac-1 may suppress HGF-induced phosphorylation of ERK and paxillin (at Ser178) and upregulate phosphorylation of paxillin at Tyr31. Based on shRNA technique, PKC? and ? were responsible for suppressing HGF-induced phosphorylation of ERK and paxillin (at Ser178), whereas PKC ? and ? were required for phosphorylation of paxillin at Tyr31. The HGF-induced fluctuant signaling is reminiscent of c-Met endocytosis. Using Concanavalin A, an inhibitor of endocytosis, we found that c-Met endocytosis was required for PKC to suppress ERK phosphorylation. Moreover, HGF-induced c-Met degradation was also fluctuant, which can be prevented by Bisindolymaleimide. In conclusion, PKC is critical for mediating HGF-induced fluctuant ERK-paxillin signaling during cell migration, probably via triggering endosomal degradation of c-Met.
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The non-coding RNA llme23 drives the malignant property of human melanoma cells.
J Genet Genomics
PUBLISHED: 02-25-2013
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Several lines of evidence support the notion that increased RNA-binding ability of polypyrimidine tract-binding (PTB) protein-associated splicing factor (PSF) and aberrant expression of long non-coding RNAs (lncRNAs) are associated with mouse and human tumors. To identify the PSF-binding lncRNA involved in human oncogenesis, we screened a nuclear RNA repertoire of human melanoma cell line, YUSAC, through RNA-SELEX affinity chromatography. A previously unreported lncRNA, termed as Llme23, was found to bind immobilized PSF resin. The specific binding of Llme23 to both recombinant and native PSF protein was confirmed in vitro and in vivo. The expression of PSF-binding Llme23 is exclusively detected in human melanoma lines. Knocking down Llme23 remarkably suppressed the malignant property of YUSAC cells, accompanied by the repressed expression of proto-oncogene Rab23. These results may indicate that Llme23 can function as an oncogenic RNA and directly associate the PSF-binding lncRNA with human melanoma.
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Histopathological classification and location of consecutively operated meningiomas at a single institution in China from 2001 to 2010.
Chin. Med. J.
PUBLISHED: 02-21-2013
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Meningioma is one of the most common primary tumors of the central nervous system, but there are not many detailed studies on the sex, age, subtypes and locations of large series. This study was a retrospective analysis of the characteristics of meningioma cases consecutively operated on at a single institution in China from 2001 to 2010.
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Structure-activity relationship studies of pyrazolo[3,4-d]pyrimidine derivatives leading to the discovery of a novel multikinase inhibitor that potently inhibits FLT3 and VEGFR2 and evaluation of its activity against acute myeloid leukemia in vitro and in
J. Med. Chem.
PUBLISHED: 02-19-2013
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We describe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea (1), which exhibits inhibitory activity but low potency against FLT3 and VEGFR2. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis using cell- and transgenic-zebrafish-based assays led to the discovery of a number of compounds that exhibited both high potency against FLT3-driven human acute myeloid leukemia (AML) MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-based assays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (33), which exhibited the highest activity in preliminary in vivo anti-AML assays, was chosen for further anti-AML studies. The results demonstrated that compound 33 is a multikinase inhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograft mouse model, a once-daily dose of compound 33 at 10 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analyses were performed to determine the mechanism of action of compound 33.
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Clinical features and treatment of intracranial chordoid meningioma: a report of 30 cases.
Histopathology
PUBLISHED: 02-17-2013
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To discuss the clinical characteristics and prognosis of chordoid meningioma (CM).
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Automated feature set selection and its application to MCC identification in digital mammograms for breast cancer detection.
Sensors (Basel)
PUBLISHED: 02-16-2013
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We propose a fully automated algorithm that is able to select a discriminative feature set from a training database via sequential forward selection (SFS), sequential backward selection (SBS), and F-score methods. We applied this scheme to microcalcifications cluster (MCC) detection in digital mammograms for early breast cancer detection. The system was able to select features fully automatically, regardless of the input training mammograms used. We tested the proposed scheme using a database of 111 clinical mammograms containing 1,050 microcalcifications (MCs). The accuracy of the system was examined via a free response receiver operating characteristic (fROC) curve of the test dataset. The system performance for MC identifications was Az = 0.9897, the sensitivity was 92%, and 0.65 false positives (FPs) were generated per image for MCC detection.
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MiR-134 regulates the proliferation and invasion of glioblastoma cells by reducing Nanog expression.
Int. J. Oncol.
PUBLISHED: 02-13-2013
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MiR-134 is a brain-enriched miRNA that plays an essential role in the development of the embryonic stem cell-orientated differentiation to central nervous system by suppression of Nanog and neural development (including neurons, cylindraxile and dendrites) and has been shown to be downregulated in oligodendrogliomas (ODG) and glioblastomas (GBM), suggesting its possible involvement in brain tumor progression. In this study, we defined the expression and function of miR-134, which we found to be downregulated in glioma samples and the glioblastoma cell line U87 by SYBR green real-time quantitative reverse transcription-PCR (real-time PCR). Early reports have characterized Nanog as a direct target of miR-134 by a dual-luciferase reporter assay in 293T cells. In our study, overexpression of miR-134 in U87 glioblastoma cells resulted in significant downregulation of Nanog mRNA levels as well as protein levels. miR-134 overexpression reduced the proliferation, invasiveness and migration capability of U87 cells while promoted apoptosis of these cells in vitro and suppressed the growth of tumor xenografts in vivo. These findings demonstrated that miR-134 deregulation is common in human gliomas. Restoration of its function inhibits cell proliferation, invasion and migration capability and promotes apoptosis, which could be partly due to its inhibitory effect on Nanog protein expression in glioblastoma cells. MiR-134 could play an important role as a tumor suppressor relying on its direct translational attenuation of Nanog.
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Analysis of protein-protein interactions in cross-talk pathways reveals CRKL protein as a novel prognostic marker in hepatocellular carcinoma.
Mol. Cell Proteomics
PUBLISHED: 02-08-2013
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Deciphering the network of signaling pathways in cancer via protein-protein interactions (PPIs) at the cellular level is a promising approach but remains incomplete. We used an in situ proximity ligation assay to identify and quantify 67 endogenous PPIs among 21 interlinked pathways in two hepatocellular carcinoma (HCC) cells, Huh7 (minimally migratory cells) and Mahlavu (highly migratory cells). We then applied a differential network biology analysis and determined that the novel interaction, CRKL-FLT1, has a high centrality ranking, and the expression of this interaction is strongly correlated with the migratory ability of HCC and other cancer cell lines. Knockdown of CRKL and FLT1 in HCC cells leads to a decrease in cell migration via ERK signaling and the epithelial-mesenchymal transition process. Our immunohistochemical analysis shows high expression levels of the CRKL and CRKL-FLT1 pair that strongly correlate with reduced disease-free and overall survival in HCC patient samples, and a multivariate analysis further established CRKL and the CRKL-FLT1 as novel prognosis markers. This study demonstrated that functional exploration of a disease network with interlinked pathways via PPIs can be used to discover novel biomarkers.
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Pin1-Nanog expression in human glioma is correlated with advanced tumor progression.
Oncol. Rep.
PUBLISHED: 01-27-2013
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The stemness gene Nanog has been shown to play an important role in tumor development, including glioma. Nanog is phosphorylated at multiple Ser/Thr-Pro motifs, which promotes the interaction between Nanog and the prolyl isomerase Pin1, leading to Nanog stabilization by suppressing its ubiquitination. The present study investigated the expression and relationship of Pin1 and Nanog in human gliomas. Significantly higher mRNA and protein expression levels of Pin1 and Nanog were demonstrated in 120 glioma specimens of different pathological grades by RT-PCR, immunohistochemistry staining and western blot analysis. The relative levels of Pin1 expression, as well as Nanog expression, were significantly positively correlated with pathological grade. Moreover, a positive correlation of Pin1 and Nanog expression in human gliomas was noted. Co-localization of Pin1 and Nanog was observed in the perinuclear space in the cytoplasm of glioma cells detected by immunofluorescence staining. Significantly positive correlation between Pin1 and Nanog in gliomas indicated that Pin1 and Nanog may be related to tumorigenesis and development of glioma cells.
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Akt1 mediates neuronal differentiation in zebrafish via a reciprocal interaction with notch signaling.
PLoS ONE
PUBLISHED: 01-14-2013
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Akt1 is well known for its role in regulating cell proliferation, differentiation, and apoptosis and is implicated in tumors and several neurological disorders. However, the role of Akt1 in neural development has not been well defined. We have isolated zebrafish akt1 and shown that this gene is primarily transcribed in the developing nervous system, and its spatiotemporal expression pattern suggests a role in neural differentiation. Injection of akt1 morpholinos resulted in loss of neuronal precursors with a concomitant increase in post-mitotic neurons, indicating that knockdown of Akt1 is sufficient to cause premature differentiation of neurons. A similar phenotype was observed in embryos deficient for Notch signaling. Both the ligand (deltaA) and the downstream target of Notch (her8a) were downregulated in akt1 morphants, indicating that Akt1 is required for Delta-Notch signaling. Furthermore, akt1 expression was downregulated in Delta-Notch signaling-deficient embryos and could be induced by constitutive activation of Notch signaling. In addition, knockdown of Akt1 was able to nullify the inhibition of neuronal differentiation caused by constitutive activation of Notch signaling. Taken together, these results provide in vivo evidence that Akt1 interacts with Notch signaling reciprocally and provide an explanation of why Akt1 is essential for the inhibition of neuronal differentiation.
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Diagnostic value of tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions.
Cancer Cytopathol
PUBLISHED: 01-05-2013
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Cytology fails to detect neoplastic cells in approximately 40% to 50% of malignant pleural effusions (PEs), which commonly accompany lung adenocarcinomas. The diagnostic accuracy of various tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions (LAC-CNPEs) has been poor. The current study attempted to maximize diagnostic efforts in distinguishing LAC-CNPEs from benign PEs.
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Arrhythmia identification with two-lead electrocardiograms using artificial neural networks and support vector machines for a portable ECG monitor system.
Sensors (Basel)
PUBLISHED: 01-04-2013
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An automatic configuration that can detect the position of R-waves, classify the normal sinus rhythm (NSR) and other four arrhythmic types from the continuous ECG signals obtained from the MIT-BIH arrhythmia database is proposed. In this configuration, a support vector machine (SVM) was used to detect and mark the ECG heartbeats with raw signals and differential signals of a lead ECG. An algorithm based on the extracted markers segments waveforms of Lead II and V1 of the ECG as the pattern classification features. A self-constructing neural fuzzy inference network (SoNFIN) was used to classify NSR and four arrhythmia types, including premature ventricular contraction (PVC), premature atrium contraction (PAC), left bundle branch block (LBBB), and right bundle branch block (RBBB). In a real scenario, the classification results show the accuracy achieved is 96.4%. This performance is suitable for a portable ECG monitor system for home care purposes.
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Protein phosphorylation profiling using an in situ proximity ligation assay: phosphorylation of AURKA-elicited EGFR-Thr654 and EGFR-Ser1046 in lung cancer cells.
PLoS ONE
PUBLISHED: 01-03-2013
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The epidermal growth factor receptor (EGFR), which is up-regulated in lung cancer, involves the activation of mitogenic signals and triggers multiple signaling cascades. To dissect these EGFR cascades, we used 14 different phospho-EGFR antibodies to quantify protein phosphorylation using an in situ proximity ligation assay (in situ PLA). Phosphorylation at EGFR-Thr654 and -Ser1046 was EGF-dependent in the wild-type (WT) receptor but EGF-independent in a cell line carrying the EGFR-L858R mutation. Using a ProtoAarray™ containing ?5000 recombinant proteins on the protein chip, we found that AURKA interacted with the EGFR-L861Q mutant. Moreover, overexpression of EGFR could form a complex with AURKA, and the inhibitors of AURKA and EGFR decreased EGFR-Thr654 and -Ser1046 phosphorylation. Immunohistochemical staining of stage I lung adenocarcinoma tissues demonstrated a positive correlation between AURKA expression and phosphorylation of EGFR at Thr654 and Ser1046 in EGFR-mutant specimens, but not in EGFR-WT specimens. The interplay between EGFR and AURKA provides an explanation for the difference in EGF dependency between EGFR-WT and EGFR-mutant cells and may provide a new therapeutic strategy for lung cancer patients carrying EGFR mutations.
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Dner inhibits neural progenitor proliferation and induces neuronal and glial differentiation in zebrafish.
Dev. Biol.
PUBLISHED: 01-02-2013
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Delta/notch-like epidermal growth factor (EGF)-related receptor (DNER) is a single-pass transmembrane protein found to be a novel ligand in the Notch signaling pathway. Its function was previously characterized in the developing cerebellum and inner ear hair cells. In this study, we isolated a zebrafish homolog of DNER and showed that this gene is expressed in the developing nervous system. Overexpression of dner or the intracellular domain of dner was sufficient to inhibit the proliferation of neural progenitors and induce neuronal and glial differentiation. In contrast, the knockdown of endogenous Dner expression using antisense morpholino oligonucleotides increased the proliferation of neural progenitors and maintained neural cells in a progenitor status through inhibition of neuronal and glial differentiation. Through analysis of the antagonistic effect on the Delta ligand and the role of the potential downstream mediator Deltex1, we showed that Dner acts in Notch-dependent and Notch-independent manner. This is the first study to demonstrate a role for Dner in neural progenitors and neuronal differentiation and provides new insights into mediation of neuronal development and differentiation by the Notch signaling pathway.
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Cytochrome p450 metabolism of betel quid-derived compounds: implications for the development of prevention strategies for oral and pharyngeal cancers.
ScientificWorldJournal
PUBLISHED: 01-01-2013
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Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) "barcodes"), and effective treatments for BQ-related oral disorders.
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Immune-related transcriptome of Coptotermes formosanus Shiraki workers: the defense mechanism.
PLoS ONE
PUBLISHED: 01-01-2013
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Formosan subterranean termites, Coptotermes formosanus Shiraki, live socially in microbial-rich habitats. To understand the molecular mechanism by which termites combat pathogenic microbes, a full-length normalized cDNA library and four Suppression Subtractive Hybridization (SSH) libraries were constructed from termite workers infected with entomopathogenic fungi (Metarhizium anisopliae and Beauveria bassiana), Gram-positive Bacillus thuringiensis and Gram-negative Escherichia coli, and the libraries were analyzed. From the high quality normalized cDNA library, 439 immune-related sequences were identified. These sequences were categorized as pattern recognition receptors (47 sequences), signal modulators (52 sequences), signal transducers (137 sequences), effectors (39 sequences) and others (164 sequences). From the SSH libraries, 27, 17, 22 and 15 immune-related genes were identified from each SSH library treated with M. anisopliae, B. bassiana, B. thuringiensis and E. coli, respectively. When the normalized cDNA library was compared with the SSH libraries, 37 immune-related clusters were found in common; 56 clusters were identified in the SSH libraries, and 259 were identified in the normalized cDNA library. The immune-related gene expression pattern was further investigated using quantitative real time PCR (qPCR). Important immune-related genes were characterized, and their potential functions were discussed based on the integrated analysis of the results. We suggest that normalized cDNA and SSH libraries enable us to discover functional genes transcriptome. The results remarkably expand our knowledge about immune-inducible genes in C. formosanus Shiraki and enable the future development of novel control strategies for the management of Formosan subterranean termites.
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Papillary meningioma: clinical and histopathological observations.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2013
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Papillary meningioma is a rare subtype of malignant meningiomas, which is classified by the World Health Organization as Grade III. Because of lack of large sample size case studies, many of the specific characteristics of papillary meningioma are unclear. This study investigated by retrospective analysis the clinical, radiological and histopathological findings of 17 papillary meningioma patients who underwent surgical resection or biopsy, to assess the characteristics of papillary meningioma. Eight female and nine male patients were included, with a mean age of 40 (range: 6 to 55) years. Tumors were mostly located in the cerebral convexity and showed irregular margins, absence of a peritumoral rim, heterogeneous enhancement and severe peritumoral brain edema on preoperative images. Brain invasion was often confirmed during the operations, with abundant to exceedingly abundant blood supply. Intratumoral necrosis and mitosis was frequently observed on routinely stained sections. The average MIB-1 labeling index was 6.9%. Seven cases experienced tumor recurrence or progression, while seven patients died 6 to 29 months after operation. Radiation therapy was given in 52.9% of all cases. Univariate analysis showed that only the existence of intratumoral necrosis and incomplete resection correlated with tumor recurrence. The 3-year progression free survival was 66.7% after gross total resection and 63.6% for other cases. The 3-year mortality rate was 50% after gross total resection and 63.6% for other cases. Papillary meningioma has specific clinical and histopathological characteristics. Tumor recurrence (or progression) and mortality are common. Gross total tumor resection resulted in less recurrence and mortality.
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Mechanical analysis of indentation cracking in Al2O3/ZrO2 nanostructured laminated ceramics.
J Nanosci Nanotechnol
PUBLISHED: 11-15-2011
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Residual stress is not the only driving force for indentation cracking in Al2O3/ZrO2 laminated ceramics. An additional driving force is induced by martensitic transformation in the plastic zone beneath the indenter, whereas surface residual compressive stress controls the expansion of surface cracks. Contributions of the transformation driving force and surface residual stress are not considered in the traditional indentation and indentation-strength theory. Therefore, fracture toughness value measured by the traditional methods is usually lower than the practical one in Al2O3/ZrO2 laminated ceramics. When the improved SENB (Single edge notched beam method)-indentation-fracture method from Japanese Industrial Standard (No. JIS R 1607-1990) is used to measure fracture toughness of Al2O3/ZrO2 laminated ceramics, the value is more reliable.
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Observations on curative effect of high-frequency electric sparkle and point-injection therapy on knee osteoarthritis.
J Tradit Chin Med
PUBLISHED: 10-31-2011
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To observe the curative effect of high-frequency electric sparkle and point-injection therapy (HESPT) on knee osteoarthritis (KOA).
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Orbital solitary fibrous tumor: a clinicopathologic study of ten cases with long-term follow-up.
Acta Neurochir (Wien)
PUBLISHED: 10-13-2011
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Solitary fibrous tumor (SFT) is a rare spindle-cell benign neoplasm and located in orbit. The present research represents case reports of ten patients with orbital SFT.
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[The efficacy of intermittent pneumatic compression in the prevention of venous thromboembolism in medical critically ill patients].
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue
PUBLISHED: 09-28-2011
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To evaluate the efficacy of intermittent pneumatic compression (IPC) in the prevention of venous thromboembolism (VTE) in medical critically ill patients.
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Effects of ivabradine on the pulmonary vein electrical activity and modulation of pacemaker currents and calcium homeostasis.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 09-13-2011
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Ivabradine is a novel heart rate decreasing agent with selective and specific antagonist effects on the pacemaker current (I(f)). The aim of this study was to investigate the pharmacological effects of ivabradine on the pulmonary vein (PV) cardiomyocytes.
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A novel finding of the atrial substrate properties and long-term results of catheter ablation in chronic atrial fibrillation patients with left atrial spontaneous echo contrast.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 09-13-2011
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The atrial substrate in chronic atrial fibrillation (AF) patients with a left atrial spontaneous echo contrast (LASEC) has not been previously reported. The aim of this study was to investigate the atrial substrate properties and long-term follow-up results in the patients who received catheter ablation of chronic AF.
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Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis.
Toxicol. Appl. Pharmacol.
PUBLISHED: 08-17-2011
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CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3,4-dimethoxyflavone, ?-naphthoflavone, and ?-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the -121/-106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3,4-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3,4-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1 expression.
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Pigment epithelium-derived factor (PEDF) promotes tumor cell death by inducing macrophage membrane tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
J. Biol. Chem.
PUBLISHED: 08-16-2011
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Pigment epithelium-derived factor (PEDF) is an intrinsic anti-angiogenic factor and a potential anti-tumor agent. The tumoricidal mechanism of PEDF, however, has not been fully elucidated. Here we report that PEDF induces the apoptosis of TC-1 and SK-Hep-1 tumor cells when they are cocultured with bone marrow-derived macrophages (BMDMs). This macrophage-mediated tumor killing is prevented by blockage of TNF-related apoptosis-inducing ligand (TRAIL) following treatment with the soluble TRAIL receptor. PEDF also increases the amount of membrane-bound TRAIL on cultured mouse BMDMs and on macrophages surrounding subcutaneous tumors. PEDF-induced tumor killing and TRAIL induction are abrogated by peroxisome proliferator-activated receptor ? (PPAR?) antagonists or small interfering RNAs targeting PPAR?. PEDF also induces PPAR? in BMDMs. Furthermore, the activity of the TRAIL promoter in human macrophages is increased by PEDF stimulation. Chromatin immunoprecipitation and DNA pull-down assays confirmed that endogenous PPAR? binds to a functional PPAR-response element (PPRE) in the TRAIL promoter, and mutation of this PPRE abolishes the binding of the PPAR?-RXR? heterodimer. Also, PPAR?-dependent transactivation and PPAR?-RXR? binding to this PPRE are prevented by PPAR? antagonists. Our results provide a novel mechanism for the tumoricidal activity of PEDF, which involves tumor cell killing via PPAR?-mediated TRAIL induction in macrophages.
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Hydralazine-induced promoter demethylation enhances sarcoplasmic reticulum Ca2+ -ATPase and calcium homeostasis in cardiac myocytes.
Lab. Invest.
PUBLISHED: 07-11-2011
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Sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) plays an essential role in Ca(2+) homeostasis and cardiac functions. The promoter region of SERCA2a has a high content of CpG islands; thus, epigenetic modification by inhibiting methylation can enhance SERCA2a expression in cardiomyocytes. Hydralazine, a drug frequently used in heart failure, is a potential DNA methylation inhibitor. We evaluated whether hydralazine can modulate Ca(2+) handling through an increase in SERCA2a expression via regulating methylation. We used indo-1 fluorescence, real-time RT-PCR, immunoblotting, and methylation-specific PCR to investigate intracellular Ca(2+), the expressions of RNA and protein, and methylation of SERCA2a in HL-1 cardiomyocytes with and without (control) the administration of hydralazine (1, 10, and 30 ?M) for 72 h. Hydralazine (10 and 30 ?M) increased the intracellular Ca(2+) transients and SR Ca(2+) contents. Hydralazine (10 and 30 ?M) decreased methylation in the SERCA2a promoter region and increased the RNA and protein expressions of SERCA2a. Additionally, hydralazine (10 and 30 ?M) decreased the expression of DNA methyltransferase 1. Moreover, treatment with hydralazine in isoproterenol-induced heart failure rats decreased the promoter methylation of SERCA2a and increased SERCA2a RNA expression. In conclusion, hydralazine-induced promoter demethylation may improve cardiac function through increasing SERCA2a and modulating calcium homeostasis in cardiomyocytes.
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L-securinine induced the human colon cancer SW480 cell autophagy and its molecular mechanism.
Fitoterapia
PUBLISHED: 06-20-2011
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To investigate the anti-tumor effects of L-securinine inducing colon cancer SW480 cell autophagy and explore its potential molecular mechanism.
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Inhibition of the P2X7 receptor reduces cystogenesis in PKD.
J. Am. Soc. Nephrol.
PUBLISHED: 06-02-2011
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The P2X7 receptor participates in purinergic signaling, which may promote the progression of ADPKD. We examined the effects of a P2X7 receptor antagonist and a P2X7 receptor agonist on cyst development in a zebrafish model of polycystic kidney disease in which we knocked down pkd2 by morpholinos. We used live wt-1b pronephric-specific GFP-expressing zebrafish embryos to directly observe changes in the pronephros. Exposure of pkd2-morphant zebrafish to a P2X7 receptor antagonist (oxidized ATP [OxATP]) significantly reduced the frequency of the cystic phenotype compared with either exposure to a P2X7 receptor agonist (BzATP) or with no treatment (P < 0.01). Histology confirmed improvement of glomerular cysts in OxATP-treated pkd2 morphants. OxATP also reduced p-ERK activity and cell proliferation in pronephric kidneys in pkd2 morphants. Inhibition of P2X7 with an additional specific antagonist (A-438079), and through morpholino-mediated knockdown of p2rx7, confirmed these effects. In conclusion, blockade of the P2X7 receptor reduces cyst formation via ERK-dependent pathways in a zebrafish model of polycystic kidney disease, suggesting that P2X7 antagonists may have therapeutic potential in ADPKD.
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Solitary fibrous tumor of the central nervous system: a clinicopathologic study of 24 cases.
Acta Neurochir (Wien)
PUBLISHED: 05-31-2011
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Solitary fibrous tumor is a rare, spindle-cell benign mesenchymal neoplasm and has a high recurrence rate. In this study, we reviewed our experience in the diagnosis and treatment of 24 patients with central nervous system solitary fibrous tumors.
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The hemorheological mechanisms in normal tension glaucoma.
Curr. Eye Res.
PUBLISHED: 05-24-2011
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To investigate the differences in hemorheological parameters between patients with normal tension glaucoma (NTG) and normal controls.
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Intracranial clear cell meningioma: a clinicopathologic study of 15 cases.
Acta Neurochir (Wien)
PUBLISHED: 05-16-2011
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Clear cell meningioma (CCM) is a rare histological variant of meningioma. CCM has a high recurrence rate and aggressiveness. In this study, we reviewed our experience in the treatment of the lesion.
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In vivo confocal microscopy of combined pre-descemet membrane corneal dystrophy and fuchs endothelial dystrophy.
Cornea
PUBLISHED: 05-11-2011
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To report the in vivo confocal microscopy (CM) findings of a patient with combined pre-Descemet membrane corneal dystrophy and Fuchs endothelial dystrophy.
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Leptin increases motility and integrin up-regulation in human prostate cancer cells.
J. Cell. Physiol.
PUBLISHED: 04-16-2011
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Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to distant organs. Leptin, an adipocyte-derived cytokine that is closely associated with obesity, has recently been shown to be involved in carcinogenesis and cancer progression. The aim of this study was to investigate whether leptin is associated with the motility of prostate cancer cells. We found that leptin increased the migration of human prostate cancer cells and expression of ?v?3 integrin on these cells. Leptin-mediated migration and increased integrin expression were attenuated by OBRl receptor antisense oligonucleotide (ODN). Activation of insulin receptor substrate (IRS-1), phosphatidylinositol 3-kinase (PI3K), Akt, and NF-?B pathways after leptin treatment was demonstrated. Furthermore, leptin-induced integrin expression and migration activity were inhibited by specific inhibitors; small interfering RNAs (siRNAs); and mutants of the IRS-1, PI3K, Akt, and NF-?B cascades. Therefore, this study shows that leptin stimulates the migration of human prostate cancer cells, one of the mechanisms underlying leptin-directed migration was transcriptional up-regulation of ?v?3 integrin expression through the OBR1/IRS-1/PI3K/Akt/NF-?B signal transduction pathway.
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Regulation of human CYP11B1 and CYP11B2 promoters by transposable elements and conserved cis elements.
Steroids
PUBLISHED: 04-13-2011
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CYP11B1 and CYP11B2 responsible for the final steps of cortisol and aldosterone synthesis, respectively, are believed to be duplicate genes with distinctive promoters. Our sequence analysis uncovers that these two genes share great homology in the proximal upstream regions, but insertion of Alu and L1 elements drives promoters divergent. Each CYP11B promoter contains two Alu elements embedded in a truncated L1 element, breaking L1 into three disconnected fragments. Alu functions as an enhancer in both genes regardless of orientation and copy number. Insertion of Alu upstream of a SV40 promoter also elevates promoter activity. However, the effect of Alu on CYP11B1 is blocked by a second L1 element (CYP11B1-L1.2) inserted between the first one and the conserved proximal upstream region. Although CYP11B1-L1.2 is 5-truncated and lacks a functional ORF, replacing it with a fluorescent gene demonstrates that the element can be transcribed from the CYP11B1 core promoter in an opposite direction and a smaller magnitude compared to CYP11B1. Deletion of CYP11B1-L1.2 greatly increases CYP11B1 promoter activity and restores the enhancing effect of Alu. The Ad5 and SF-1 binding elements conserved in the proximal core promoter play a role in basal expression of both genes. Mutation of the Ad5 site reduces promoter activity to the minimal level. ERR? is the transcription factor interacting with Ad5 during basal expression. The core promoters of both genes are also conserved in mouse and rat despite the fact that the sites corresponding to cre, Ad5, and SF-1 in rodent Cyp11b1 promoters deviate from consensus.
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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.

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

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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.