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Find video protocols related to scientific articles indexed in Pubmed.
Enhancement of the field emission from the TiO2 nanotube arrays by reducing in a NaBH4 solution.
ACS Appl Mater Interfaces
PUBLISHED: 11-20-2014
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A mass of oxygen vacancies are successfully introduced into TiO2 nanotube arrays using low-cost NaBH4 as a reductant in a liquid-phase environment. By controlling and adjusting the reduction time over the range of 0-24 h, the doping concentration of the oxygen vacancy realizes controllable and eventually reaches saturation. Meanwhile, the thermal stability of oxygen vacancies is also investigated, indicating that part of oxygen vacancies remain stable up to 250 °C. In addition, this liquid-phase reduction strategy significantly lowers the requirements of instruments and cost. More interesting, reduced TiO2 nanotube arrays show drastically enhanced field emission performances including substantially decreased turn-on field from 25.01 to 2.65 V/?m, a high current density of 3.5 mA/cm2 at 7.2 V/?m and an excellent field emission stability and repeatability. These results are attributed to the oxygen vacancies obtained by reducing in NaBH4 solution, resulting in a reduced effective work function and an increased conductivity.
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Ultrasensitive, self-calibrated cavity ring-down spectrometer for quantitative trace gas analysis.
Appl Opt
PUBLISHED: 11-18-2014
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A cavity ring-down spectrometer is built for trace gas detection using telecom distributed feedback (DFB) diode lasers. The longitudinal modes of the ring-down cavity are used as frequency markers without active-locking either the laser or the high-finesse cavity. A control scheme is applied to scan the DFB laser frequency, matching the cavity modes one by one in sequence and resulting in a correct index at each recorded spectral data point, which allows us to calibrate the spectrum with a relative frequency precision of 0.06 MHz. Besides the frequency precision of the spectrometer, a sensitivity (noise-equivalent absorption) of 4×10-11??cm-1??Hz-1/2 has also been demonstrated. A minimum detectable absorption coefficient of 5×10-12??cm-1 has been obtained by averaging about 100 spectra recorded in 2  h. The quantitative accuracy is tested by measuring the CO2 concentrations in N2 samples prepared by the gravimetric method, and the relative deviation is less than 0.3%. The trace detection capability is demonstrated by detecting CO2 of ppbv-level concentrations in a high-purity nitrogen gas sample. Simple structure, high sensitivity, and good accuracy make the instrument very suitable for quantitative trace gas analysis.
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Theoretical insights into nucleation of CO2 and CH4 hydrates for CO2 capture and storage.
Phys Chem Chem Phys
PUBLISHED: 11-07-2014
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We present a hybrid three-dimensional (3D) theoretical approach, the density functional theory (DFT) integrated with the reference interaction site model (RISM), to investigate the nucleation of CO2 and CH4 hydrates. Within the theoretical framework, the 3D-RISM is applied to describe gas density distributions in hydrate cages, and the 3D-DFT is used to describe the interfacial structure and properties of the two hydrates, as well as their nucleation. The crystal-liquid phase equilibria of CO2 and CH4 hydrates are predicted by the hybrid 3D-DFT-RISM, and compared with the available experimental data to examine the theoretical model. In particular, the local and interfacial structure and properties, the critical nucleus radii and free-energy barriers at moderate concentration supersaturation are presented to analyze their nucleation. The formation enthalpies for the two hydrates are calculated to evaluate the possibility of CO2 storage by CH4-CO2 replacement in hydrate.
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NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development.
Genes Dev.
PUBLISHED: 11-05-2014
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Cerebellar development is regulated by a coordinated spatiotemporal interplay between granule neuron progenitors (GNPs), Purkinje neurons, and glia. Abnormal development can trigger motor deficits, and more recent data indicate important roles in aspects of memory, behavior, and autism spectrum disorders (ASDs). Germline mutation in the NF1 tumor suppressor gene underlies Neurofibromatosis type 1, a complex disease that enhances susceptibility to certain cancers and neurological disorders, including intellectual deficits and ASD. The NF1 gene encodes for neurofibromin, a RAS GTPase-activating protein, and thus negatively regulates the RAS signaling pathway. Here, using mouse models to direct conditional NF1 ablation in either embryonic cerebellar progenitors or neonatal GNPs, we show that neurofibromin is required for appropriate development of cerebellar folia layering and structure. Remarkably, neonatal administration of inhibitors of the ERK pathway reversed the morphological defects. Thus, our findings establish a critical cell-autonomous role for the NF1-RAS-ERK pathway in the appropriate regulation of cerebellar development and provide a basis for using neonatal ERK inhibitor-based therapies to treat NF1-induced cerebellar disorders.
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Organocatalytic Diversity-Oriented Asymmetric Synthesis of Tricyclic Chroman Derivatives.
J. Org. Chem.
PUBLISHED: 10-30-2014
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The tandem oxo-Michael-IED/HDA and oxo-Michael-IED/HDA-Michael-Aldol condensation transformations between (E)-2-hydroxyaryl-2-oxobut-3-enoate derivatives with enals have been developed in the presence of (S)-diphenylprolinol trimethylsilyl ether as an organocatalyst. Two types of tricyclic chroman derivatives were, respectively, obtained, by adjusting the reactant ratio and reaction temperature, in good yields (up to 96%) with excellent enantioselectivities (up to >99%) and good diastereoselectivities (up to >30/1). It should be noted that the divergent chiral chroman derivatives were obtained by successive reaction of (E)-2-hydroxyaryl-2-oxobut-3-enoate derivatives with two different enal substrates in highly catalytic results.
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FDG PET/CT Findings of Malignant Fibrous Histiocytoma of the Stomach.
Clin Nucl Med
PUBLISHED: 10-28-2014
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A 22-year-old man underwent an FDG PET/CT scan to evaluate possible malignancy due to melena and fever for 1 month. The images demonstrated intense FDG activity with an SUVmax of 24.6 in a large mass in the fundus of the stomach. Gastric malignant fibrous histiocytoma was histopathologically confirmed. Malignant fibrous histiocytoma is a high-grade and aggressive sarcoma, which usually occurs in the limbs or retroperitoneum. Malignant fibrous histiocytoma in the stomach is rare.
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Long-term outcome of high-risk prostate cancer treated with brachytherapy combined with external-beam radiation therapy and androgen deprivation therapy.
Tumori
PUBLISHED: 10-25-2014
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Aims and background. To evaluate long-term outcome and biochemical progression-free survival (bPFS) in high-risk prostate cancer patients treated with brachytherapy combined with external-beam radiation therapy (EBRT) and androgen deprivation therapy (ADT). Methods and study design. We retrospectively analyzed 97 high-risk prostate cancer patients treated with brachytherapy combined with EBRT and ADT. During follow-up, the post-operation prostate-specific antigen (PSA) level was monitored regularly and biochemical relapse, progression to castration-resistant prostate cancer or metastases, and causes of death were documented. We evaluated bPFS, cause-specific survival (CSS) and overall survival (OS). Results. The bPFS, CSS and OS of the patients were 81.4%, 88.7% and 81.4%, respectively. The bPFS of the subcategories of patients stratified based on the presence or absence of a Gleason pattern 5 were 55.6% and 87.7%, respectively. Conclusion. Brachytherapy combined with EBRT and ADT can effectively control PSA level and delay biochemical relapse in localized high-risk prostate cancer. However, patients presenting with a Gleason pattern 5 should be managed with further treatment intensification.
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Luminescence Properties and Energy Transfer of Eu/Mn-Coactivated Mg2Al4Si5O18 as a Potential Phosphor for White-Light LEDs.
Inorg Chem
PUBLISHED: 10-17-2014
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A series of blue-to-white emitting Mg2Al4Si5O18: Eu(2+), Mn(2+) phosphors were synthesized via high-temperature solid-state method, and their luminescence properties were investigated in detail. Under near-ultraviolet (UV) light excitation of 365 nm, Eu(2+)-doped Mg2Al4Si5O18 exhibits a broad blue emission band peaked at 469 nm, and Mn(2+)-doped Mg2Al4Si5O18 shows a broad orange-red emission band near 600 nm. The energy transfer from Eu(2+) to Mn(2+) in Mg2Al4Si5O18 host matrix can be found, and the resonant type is demonstrated by a dipole-quadrupole mechanism. The emission hue can be tuned from blue (0.17, 0.17) to bluish green (0.22, 0.29) and finally to white (0.31, 0.33) by properly varying the ratio of Eu(2+)/Mn(2+). The thermal quenching property of the sample was investigated, and the activation energy ?E was estimated to be 0.30 eV. Additionally, the energy transfer critical distance between Eu(2+) and Mn(2+) was calculated. With appropriate tuning of activator content, the Mg2Al4Si5O18: Eu(2+), Mn(2+) phosphor may have potential application for UV light-emitting diodes.
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Introduction on the fabrication technique of phosphor in glass by tape-casting and investigation on the chromaticity property.
Opt Express
PUBLISHED: 10-17-2014
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We introduce a new fabrication technique of phosphor in glass (PiG) for light-emitting diodes (LEDs) employing the tape-casting. Through the detailed process described herein and the measurement results, it is clear that the PiG-on-glass not only share the same characteristic of those obtained from other techniques or the bulk PiG, but with more precisely controlled width from a few to hundreds micrometers. The samples are mounted on blue InGaN LED chips to test the color properties of the white light. Besides, we established an empirical model that could predict the final color properties of LEDs solely by the phosphor concentration of phosphor glass under certain conditions. This model would greatly facilitate the design of PiG-based LEDs.
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Rosuvastatin may reduce the incidence of cardiovascular events in patients with acute coronary syndromes receiving acute coronary syndromes by suppressing miR-155/SHIP-1 signaling pathway.
Cardiovasc Ther
PUBLISHED: 10-17-2014
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The benefical effect of rosuvastatin against percutaneous coronary intervention (PCI) related procedural myocardial injury has been determined mostly in patients with acute coronary syndromes (ACS). However, the detailed therapeutic mechanism has not been well studied.
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The effect of a microcatheter-based selective intra-arterial hypothermia on hemodynamic changes following transient cerebral ischemia.
Neurol. Res.
PUBLISHED: 10-14-2014
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Objectives: We investigated the effect of a microcatheter-based selectively induced intra-arterial hypothermia on hemodynamic changes following transient cerebral ischemia in rats. Methods: Stroke was induced in male Sprague-Dawley rats by a two-hour middle cerebral artery occlusion (MCAO) using a microcatheter. After the two-hour MCAO, 0·9% cold saline (0°C) was selectively infused through a microcatheter. Cerebral blood flow (CBF) in the ischemic brain region was continuously monitored by Laser-Doppler flowmetry (LDF) during the procedure. Following ischemia/reperfusion, serial functional neurologic testing was performed, and cerebral infarct volume was evaluated after 48 hours. Results: The local cold saline infusion, via a microcatheter, achieved a rapid induction of brain hypothermia (cerebral cortex from 37·1 ± 0·3 to 30·7 ± 0·4°C; striatum from 37·5 ± 0·3 to 30·9 ± 0·5°C). When compared to the non-treatment group, the local cold saline infusion treatment reduced both post-ischemic hyperperfusion (about 40%, P < 0·01) and delayed post-ischemic hypoperfusion (P < 0·01), improved functional neurological testing (P < 0·01), and reduced both cerebral infarction volume (40·6 ± 5·3 vs. 61·7 ± 8·6%, P < 0·01) and cerebral edema (7·8 ± 2·6 vs.15·4 ± 3·2%, P < 0·01). Conclusion: Cold saline, when infused directly into the ischemic brain region, can confer robust neuroprotection by reducing immediate post-ischemic hyperperfusion and delayed post-ischemic hypoperfusion.
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Decreasing GSH and increasing ROS in chemosensitivity gliomas with IDH1 mutation.
Tumour Biol.
PUBLISHED: 10-05-2014
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Gliomas are the most malignant and aggressive primary brain tumor in adults. Despite concerted efforts to improve therapies, their prognosis remains very poor. Isocitrate dehydrogenase 1 (IDH1) mutations have been discovered frequently in glioma patients and are strongly correlated with improved survival. However, the effect of IDH1 mutations on the chemosensitivity of gliomas remains unclear. In this study, we generated clonal U87 and U251 glioma cell lines overexpressing the R132H mutant protein (IDH1-R132H). Compared with control cells and cells overexpressing IDH wild type (IDH1-WT), both types of IDH1-R132H cells were more sensitive to temozolomide (TMZ) and cis-diamminedichloroplatinum (CDDP) in a time- and dose-dependent manner. The IDH1-R132H-induced higher chemosensitivity was associated with nicotine adenine disphosphonucleotide (NADPH), glutathione (GSH) depletion, and reactive oxygen species (ROS) generation. Accordingly, this IDH1-R132H-induced growth inhibition was effectively abrogated by GSH in vitro and in vivo. Our study provides direct evidence that the improved survival in patients with IDH1-R132H tumors may partly result from the effects of the IDH1-R132H protein on chemosensitivity. The primary cellular events associated with improved survival are the GSH depletion and increased ROS generation.
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Arabidopsis PHOSPHOTYROSYL PHOSPHATASE ACTIVATOR Is Essential for PROTEIN PHOSPHATASE 2A Holoenzyme Assembly and Plays Important Roles in Hormone Signaling, Salt Stress Response, and Plant Development.
Plant Physiol.
PUBLISHED: 10-03-2014
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PROTEIN PHOSPHATASE 2A (PP2A) is a major group of serine/threonine protein phosphatases in eukaryotes. It is composed of three subunits: scaffolding subunit A, regulatory subunit B, and catalytic subunit C. Assembly of the PP2A holoenzyme in Arabidopsis (Arabidopsis thaliana) depends on Arabidopsis PHOSPHOTYROSYL PHOSPHATASE ACTIVATOR (AtPTPA). Reduced expression of AtPTPA leads to severe defects in plant development, altered responses to abscisic acid, ethylene, and sodium chloride, and decreased PP2A activity. In particular, AtPTPA deficiency leads to decreased methylation in PP2A-C subunits (PP2Ac). Complete loss of PP2Ac methylation in the suppressor of brassinosteroid insensitive1 mutant leads to 30% reduction of PP2A activity, suggesting that PP2A with a methylated C subunit is more active than PP2A with an unmethylated C subunit. Like AtPTPA, PP2A-A subunits are also required for PP2Ac methylation. The interaction between AtPTPA and PP2Ac is A subunit dependent. In addition, AtPTPA deficiency leads to reduced interactions of B subunits with C subunits, resulting in reduced functional PP2A holoenzyme formation. Thus, AtPTPA is a critical factor for committing the subunit A/subunit C dimer toward PP2A heterotrimer formation.
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Determination of the multiple local properties of thin layer with high lateral resolution by scanning acoustic microscopy.
Rev Sci Instrum
PUBLISHED: 10-03-2014
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Simultaneous determination of the multiple local acoustic and geometrical properties of the thin layer with a high lateral resolution is of great interest in ultrasonic non-destructive evaluation. In this paper, we propose a technique based on the V(z, t) data to simultaneously determine the four local properties of the thin layer, namely, the thickness, the sound velocity, the acoustic impedance, and the density. First, the V(z, t) data are collected from both the thin layer and the reference material. Then the sound velocity and the thickness are calculated by focusing the point-focusing transducer on the front and back surfaces of the thin layer, with the confocal positions determined by averaging the peak positions in the V(z) curves at different frequencies. Second, the acoustic impedance of the thin layer is obtained based on the experimental and theoretical two-dimensional reflection spectrum using the echo from the front surface of the layer. Finally, the density can be obtained by dividing the acoustic impedance by the sound velocity. The four local properties of an aluminum layer are accurately obtained using our method. The largest relative error of determining the four properties is around 1%. This technique opens a new way of simultaneously measuring the multiple local acoustic and geometrical properties of thin layers.
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Inactivation of Corticotropin-Releasing Hormone-Induced Insulinotropic Role by High-Altitude Hypoxia.
Diabetes
PUBLISHED: 10-02-2014
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We have shown that hypoxia reduces plasma insulin, which correlates with corticotropin-releasing hormone (CRH) receptor 1 (CRHR1) in rats, but the mechanism remains unclear. Here, we report that hypobaric hypoxia at an altitude of 5,000 m for 8 h enhances rat plasma CRH, corticosterone, and glucose levels, whereas the plasma insulin and pancreatic ATP/ADP ratio is reduced. In islets cultured under normoxia, CRH stimulated insulin release in a glucose- and CRH-level-dependent manner by activating CRHR1 and thus the cAMP-dependent protein kinase pathway and calcium influx through L-type channels. In islets cultured under hypoxia, however, the insulinotropic effect of CRH was inactivated due to reduced ATP and cAMP and coincident loss of intracellular calcium oscillations. Serum and glucocorticoid-inducible kinase 1 (SGK1) also played an inhibitory role. In human volunteers rapidly ascended to 3,860 m, plasma CRH and glucose levels increased without a detectable change in plasma insulin. By contrast, volunteers with acute mountain sickness (AMS) exhibited a marked decrease in HOMA insulin sensitivity (HOMA-IS) and enhanced plasma CRH. In conclusion, hypoxia may attenuate the CRH-insulinotropic effect by reducing cellular ATP/ADP ratio, cAMP and calcium influx, and upregulated SGK1. Hypoxia may not affect HOMA-IS in healthy volunteers but reduces it in AMS volunteers.
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Work-up and management of lone atrial fibrillation: results of the European Heart Rhythm Association Survey.
Europace
PUBLISHED: 10-01-2014
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The purpose of this European Heart Rhythm Association (EHRA) survey was to explore the work-up and management of lone atrial fibrillation (AF) among the European centres. Thirty-two European centres, all members of the EHRA electrophysiology (EP) research network, responded to this survey and completed the list of questions. The prevalence of lone AF has been reported to be ?10% by 19 (60%) of the participating centres. The presence of isolated left atrial enlargement and left ventricular diastolic dysfunction represent heart disease according to 50 and 84% of the centres, respectively, and exclude the diagnosis of lone AF. Fifty-nine per cent of responders do not routinely consider genetic testing in lone AF patients. The initial therapeutic approach in symptomatic paroxysmal lone AF is antiarrhythmic drug therapy as reported by 31 (97%) of the centres. Pulmonary vein isolation only is the first ablation strategy for patients with symptomatic persistent lone AF at 27 (84%) of the responding centres. Assessment for sleep apnoea, obesity, and intensive sports activity in lone AF is performed at 27 (84%) centres. In conclusion, this EP Wire survey confirms that the term 'lone AF' is still used in daily practice. The work-up typically includes screening for known risk factors but not genetic testing. The preferred management of paroxysmal lone AF is rhythm control with antiarrhythmic drugs, whereas pulmonary vein isolation is the first ablation strategy for the majority of patients with symptomatic persistent lone AF.
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Low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus idarubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia.
Leuk. Lymphoma
PUBLISHED: 09-27-2014
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With limited data available on the low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor (CAG) regimen in newly diagnosed older patients with acute myeloid leukemia (AML), this study aimed at comparing the efficacy and toxicity of CAG with idarubicin plus cytarabine (IA) remission induction therapy in these patients. A total of 154 consecutive patients (52 with CAG and 102 with IA) were retrospectively analyzed. The patients in the CAG group had a higher median age (68 vs. 65 years, p = 0.002) and a higher proportion of previous myelodysplastic syndrome (25.0% vs. 2.9%, p < 0.0001) compared to those in the IA group. The complete remission rates with the CAG and IA regimens were 55.8% and 52.9% (p = 0.864). The median overall survival (12.1 vs. 11.7 months, p = 0.650) and 3-year disease-free survival rates (29.6% vs. 48.6%, p = 0.657) were not statistically different in the two groups. The CAG regimen might be an alternative to conventional chemotherapy in older patients with AML.
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Association of HTR2A T102C and A-1438G polymorphisms with susceptibility to major depressive disorder: a meta-analysis.
Neurol. Sci.
PUBLISHED: 09-24-2014
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Serotonin 2A receptor (HTR2A) gene was implicated to be associated with major depressive disorder (MDD) susceptibility due to its role of key neurotransmitter in many physiologic processes. A great number of related studies reported in different populations have emerged. The results of these studies, however, have been inconsistent and thereby definite conclusions are difficult to establish. With the cumulative data in recent years, it was necessary to carry out a comprehensive analysis of previous findings. Electronic databases were systematically searched for studies published before May 2013. Pooled odds ratios (OR) and 95 % confidence interval (CI) were estimated under three different genetic models. Subgroup and sensitivity analyses were also performed. A total of 21 studies, 3,299 patients and 4,092 controls, met the selection criteria. 15 studies included HTR2A T102C polymorphism (with a total of 2,409 patients and 3,130 controls), and 9 studies included HTR2A A-1438G polymorphism (with a total of 1,510 patients and 2,281 controls). Our results showed that no significant association of MDD susceptibility with T102C polymorphism was found in allelic analysis and genotypic analysis (For T vs. C: OR = 1.06, 95 % CI = 0.95-1.18, P = 0.307; For TT + TC vs. CC: OR = 1.07, 95 % CI = 0.90-1.28, P = 0.451; For TT vs. TC + CC: OR = 1.08, 95 % CI = 0.95-1.22, P = 0.235). With respect to A-1438G polymorphism, however, carriers with A allele tend to suffer from MDD (AA + AG vs. GG: OR = 1.20, 95 % CI = 1.02-1.43, P = 0.030). When stratified by race for T102C polymorphism and A-1438G polymorphism of the HTR2A, we found no significant association. In conclusions, our study suggests that the A allele of A-1438G polymorphism might play a role in susceptibility to MDD. On the contrary, T102C polymorphism does not seem to be capable of modifying MDD risk.
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[Clinical significance of TET2 gene expression in 157 adult acute myeloid leukemia patients with normal cytogenetics].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 09-24-2014
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To explore the clinical significance of ten-eleven-translocation methylcytosine dioxygenase 2 (TET2) mRNA expression levels in adult acute myeloid leukemia patients with normal cytogenetics (CN-AML).
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Nucleic Acid-induced tetraphenylethene probe noncovalent self-assembly and the superquenching of aggregation-induced emission.
Anal. Chem.
PUBLISHED: 09-22-2014
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Superquenching of aggregation-induced emission (AIE) has been utilized in biosensing for the first time. A positively charged tetraphenylethene derivative (compound 1) showed no emission in an aqueous buffer solution. A single-stranded DNA (a polyanion) induced aggregation of compound 1, and strong compound 1 aggregate emission was observed. When the DNA was labeled with a quencher molecule, compound 1 aggregate emission was efficiently quenched. On the basis of this observation, a new, simple, sensitive and selective DNA methyltransferase (MTase) assay has been developed. A quencher-labeled double-stranded DNA could induce aggregation of compound 1, and superquenching of compound 1 AIE was observed. In the presence of MTase and an endonuclease, the DNA could be specifically methylated and cleaved into single-stranded DNA fragments. The quencher molecule was released, and a turn-on emission signal was detected.
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Fine-tuning of the fatty acid pathway by synthetic antisense RNA for enhanced (2S)-naringenin production from L-tyrosine in Escherichia coli.
Appl. Environ. Microbiol.
PUBLISHED: 09-21-2014
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Malonyl coenzyme A (malonyl-CoA) is an important precursor for the synthesis of natural products, such as polyketides and flavonoids. The majority of this cofactor is often consumed for producing fatty acids and phospholipids, leaving only a small amount of cellular malonyl-CoA available for producing the target compound. Tuning of malonyl-CoA into heterologous pathways yields significant phenotypic effects, such as growth retardation and even cell death. In this study, fine-tuning of the fatty acid pathway in Escherichia coli with antisense RNA (asRNA) to balance the demands on malonyl-CoA for target-product synthesis and cell health was proposed. To establish an efficient asRNA system, the relationship between sequence and function for asRNA was explored. It was demonstrated that the gene-silencing effect of asRNA could be tuned by directing asRNA to different positions in the 5'-UTR (untranslated region) of the target gene. Based on this principle, the activity of asRNA was quantitatively tailored to balance the need for malonyl-CoA in cell growth and the production of the main flavonoid precursor, (2S)-naringenin. Appropriate inhibitory efficiency of the anti-fabB/fabF asRNA improved the production titer by 431% (391 mg/L). Therefore, the strategy presented in this study provided a useful tool for the fine-tuning of endogenous gene expression in bacteria.
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Genomic evolution of Saccharomyces cerevisiae under Chinese rice wine fermentation.
Genome Biol Evol
PUBLISHED: 09-13-2014
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Rice wine fermentation represents a unique environment for the evolution of the budding yeast, Saccharomyces cerevisiae. To understand how the selection pressure shaped the yeast genome and gene regulation, we determined the genome sequence and transcriptome of a S. cerevisiae strain YHJ7 isolated from Chinese rice wine (Huangjiu), a popular traditional alcoholic beverage in China. By comparing the genome of YHJ7 to the lab strain S288c, a Japanese sake strain K7, and a Chinese industrial bioethanol strain YJSH1, we identified many genomic sequence and structural variations in YHJ7, which are mainly located in subtelomeric regions, suggesting that these regions play an important role in genomic evolution between strains. In addition, our comparative transcriptome analysis between YHJ7 and S288c revealed a set of differentially expressed genes, including those involved in glucose transport (e.g., HXT2, HXT7) and oxidoredutase activity (e.g., AAD10, ADH7). Interestingly, many of these genomic and transcriptional variations are directly or indirectly associated with the adaptation of YHJ7 strain to its specific niches. Our molecular evolution analysis suggested that Japanese sake strains (K7/UC5) were derived from Chinese rice wine strains (YHJ7) at least approximately 2,300 years ago, providing the first molecular evidence elucidating the origin of Japanese sake strains. Our results depict interesting insights regarding the evolution of yeast during rice wine fermentation, and provided a valuable resource for genetic engineering to improve industrial wine-making strains.
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Effects of Surface Displayed Targeting Ligand GE11 on Liposome Distribution and Extravasation in Tumor.
Mol. Pharm.
PUBLISHED: 09-12-2014
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Targeting ligands displayed on liposome surface had been used to mediate specific interactions and drug delivery to target cells. However, they also affect liposome distribution in vivo, as well as the tissue extravasation processes after IV injection. In this study, we incorporated an EGFR targeting peptide GE11 on liposome surfaces in addition to PEG at different densities and evaluated their targeting properties and antitumor effects. We found that the densities of surface ligand and PEG were critical to target cell binding in vitro as well as pharmacokinetic profiles in vivo. The inclusion of GE11-PEG-DSPE and PEG-DSPE at 2% and 4% mol ratios in the liposome formulation mediated a rapid accumulation of liposomes within 1 h after IV injection in the tumor tissues surrounding neovascular structures. This is in addition to the EPR effect that was most prominently described for surface PEG modified liposomes. Therefore, despite the fact that the distribution of liposomes into interior tumor tissues was still limited by diffusion, GE11 targeted doxorubicin loaded liposomes showed significantly better antitumor activity in tumor bearing mice as a result of the fast active-targeting efficiency. We anticipate these understandings can benefit further optimization of targeted drug delivery systems for improving efficacy in vivo.
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Preliminary identification of palaeofloods with the alkane ratio C31/C17 and their potential link to global climate changes.
Sci Rep
PUBLISHED: 09-10-2014
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A major challenge in palaeohydrology is the extraction of continuous palaeoflood information from geophysical records. A high-resolution sediment core off the Minjiang estuary area in the Taiwan Strait, SE China, records the sedimentation history from approximately 1660 to the present. The alkane ratio C31/C17, a classic organic geochemical indicator of terrestrial/aquatic matter, peaks in the layers dating as 1876-1878 and 1968-1970, suggesting the large terrestrial input to the Minjiang estuary area by huge flood transporting during the each peak interval. Historical archives are consistent with this interpretations and record catastrophic floods in the Minjiang River during both intervals. Furthermore between 1876-1878 there were floods in southern China and droughts in northern China, as well as throughout Asia, Africa, Australia, and the Americas. The 1876-1878 catastrophic flood of the Minjiang River may therefore has been the local response to global climate anomalies during that time interval.
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Progression of White Matter Hyperintensities of Presumed Vascular Origin Increases the Risk of Falls in Older People.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 09-10-2014
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Greater volume of cerebral white matter hyperintensities (WMH) of presumed vascular origin may affect postural control and gait. WMH measured at one time point predicts an increased risk of incident multiple falls. However, it is unknown whether WMH progression increases falls risk. We hypothesized that the progression of WMH would be associated with a greater risk of multiple falls.
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Combination of sacral neuromodulation and tolterodine for treatment of idiopathic overactive bladder in women: a clinical trial.
Urol J
PUBLISHED: 09-06-2014
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To evaluate the efficacy of intermittent percutaneous needle sacral nerve stimulation (IPN-SNS) in women with idiopathic overactive bladder (IOAB) treated with tolterodine.
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Methods for the year 6 follow-up study of children in the Infant Feeding Practices Study II.
Pediatrics
PUBLISHED: 09-04-2014
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We describe methods used in the Year 6 Follow-Up (Y6FU) of children who participated in the Infant Feeding Practices Study II (IFPSII). This study consists of a questionnaire administered 6 years after the IFPSII to characterize the health, development, and diet quality of the children.
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Use of event recorders and loop recorders in clinical practice: results of the European Heart Rhythm Association Survey.
Europace
PUBLISHED: 08-31-2014
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Several kinds of electrocardiogram monitoring systems are now available in the clinical practice. The aim of this European Heart Rhythm Association (EHRA) survey was to assess the use of different monitoring techniques in the evaluation of patients with unexplained syncope, palpitations, and in those with established diagnosis of atrial fibrillation. Forty-five centres in Europe answered the questionnaire and the majority (78%) were university hospitals. The answers showed a discrepancy between the recommended use of implantable loop recorders (ILRs) in patients with unexplained syncope and the use of this device in clinical practice. In most of the cases only a minority of patients (<20%) seemed to actually receive an ILR as a part of the diagnostic process in accordance to the current guidelines. Holter monitoring systems and external loop recorders seemed to be the preferred monitoring techniques both in patients with recurrent palpitations and in those with established diagnosis of atrial fibrillation.
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Surface Modification of Polyacrylonitrile Fibre by Nitrile Hydratase from Corynebacterium nitrilophilus.
Appl. Biochem. Biotechnol.
PUBLISHED: 08-28-2014
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Previously, nitrile hydratase (NHase) from Corynebacterium nitrilophilus was obtained and showed potential in polyacrylonitrile (PAN) fibre modification. In the present study, the modification conditions of C. nitrilophilus NHase on PAN were investigated. In the optimal conditions, the wettability and dyeability (anionic and reactive dyes) of PAN treated by C. nitrilophilus NHase reached a similar level of those treated by alkali. In addition, the chemical composition and microscopically observable were changed in the PAN surface after NHase treatment. Meanwhile, it revealed that cutinase combined with NHase facilitates the PAN hydrolysis slightly because of the ester existed in PAN as co-monomer was hydrolyzed. All these results demonstrated that C. nitrilophilus NHase can modify PAN efficiently without textile structure damage, and this study provides a foundation for the further application of C. nitrilophilus NHase in PAN modification industry.
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Roles of tryptophan residue and disulfide bond in the variable lid region of oxidized polyvinyl alcohol hydrolase.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-27-2014
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Oxidized polyvinyl alcohol hydrolase (OPH) catalyzes the cleavage of C-C bond in ?-diketone. It belongs to the ?/?-hydrolase family and contains a unique lid region that covers the active site. The lid is the most variable region when pOPH from Pseudomonas sp. VM15C and sOPH from Sphingopyxis sp. 113P3 are compared. The wild-type enzymes and the pOPH mutants W255A, W255Y and W255F were analyzed for lipase activity by using p-nitrophenyl (pNP) esters as the substrates. The wild-type enzymes showed increased Km and decreased kcat/Km with the acyl chain length, and the mutants showed reduced kcat/Km for pNP acetate, indicating the importance of Trp255 in sequestering the active site from solvent. The significantly lower activity for pNP butyrate can be a result of product inhibition, as suggested by the complex crystal structures, in which butyric acid, DMSO or PEG occupied the same substrate-binding cleft. The mutant activity was retained with pNP caprylate and pNP laurate as the substrates, reflecting the amphipathic nature of the cleft. Moreover, the disulfide bond formation of Cys257/267 is important for the activity of pOPH, but it is not essential for sOPH, which has a shorter lid structure.
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Caffeoylquinic acid derivatives isolated from the aerial parts of Gynura divaricata and their yeast ?-glucosidase and PTP1B inhibitory activity.
Fitoterapia
PUBLISHED: 08-27-2014
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The phytochemical investigation of natural products of Gynura divaricata led to the isolation of eleven caffeoylquinic acid derivatives. They were characterized by spectrometric methods as 5-O-caffeoylquinic acid (1), 5-O-p-coumaroylquinic acid (2), 5-O-feruloylquinic acid (3), methyl 5-O-caffeoylquinate (4), 3,4-dicaffeoylquinic acid (5), 3,5-dicaffeoylquinic acid (6), 4,5-dicaffeoylquinic acid (7), methyl 3,4-dicaffeoylquinate (8), methyl 3,5-dicaffeoylquinate (9), methyl 4,5-dicaffeoylquinate (10) and ethyl 4,5-dicaffeoylquinate (11). The individual compounds were screened for the inhibition of yeast ?-glucosidase and Protein Tyrosine Phosphatase 1B (PTP1B) using in vitro assays. Among the isolated compounds, 3,4-dicaffeoylquinic acid (5), 4,5-dicaffeoylquinic acid (7), methyl 3,4-dicaffeoylquinate (8) and methyl 4,5-dicaffeoylquinate (10) exhibited significant inhibitory activities against ?-glucosidase. In addition, 5-O-p-coumaroylquinic acid (2), 3,5-dicaffeoylquinic acid (6) and 4,5-dicaffeoylquinic acid (7) had considerable inhibitory effect against PTP1B. Based on these findings, the caffeoylquinic acid derivatives were deduced to be potentially responsible for the anti-diabetic activity of G. divaricata. The preliminary structure-activity relationship study suggests that the number and positioning of caffeoyl groups in the quinic acid derivatives are important for both ?-glucosidase and PTP1B inhibitory potency. Moreover, the corresponding methyl esters of some dicaffeoylquinic acids have enhanced inhibitory activity against yeast ?-glucosidase.
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New lipophilic polyelectrolyte gels containing quaternary ammonium salt with superabsorbent capacity for organic solvents.
ACS Appl Mater Interfaces
PUBLISHED: 08-25-2014
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Water and soil pollution by organic pollutants from petrochemical plants has become one of the major environmental problems in recent years. Lipophilic polyelectrolyte gels with ionic groups dissociable in nonpolar organic solvents show an enhanced swelling ability in a corresponding media attributed to the electrostatic repulsion and osmotic pressure provided by dissociated ionic groups. Here, we synthesized new lipophilic polyelectrolyte gels based on an easily available electrolyte monomer, methacryloxyethyl dimethyloctane ammonium trifluoromethanesulfonimide (MODAT), and a lipophilic neutral monomer, dodecyl acrylate by radiation-induced polymerization and cross-linking. The resultant lipophilic polyelectrolyte gels could absorb plenty of organic solvents with dielectric constants lower than 20 and exhibited a high absorbing ability at a wide range of temperatures (0-40 °C). The maximum swelling degree could reach as high as 200 g/g in some media, such as 1,2-dichloroethane (199.4 g/g) and dichloromethane (204 g/g), which was much higher than that of the nonionic gel without the addition of MODAT. Moreover, the resultant lipophilic polyelectrolyte gels could release most of the absorbed solvents within several hours and then be reused. It is expected that this new type of lipophilic polyelectrolyte gels may be a suitable candidate as organic pollutant absorbents.
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Systems metabolic engineering of microorganisms to achieve large-scale production of flavonoid scaffolds.
J. Biotechnol.
PUBLISHED: 08-23-2014
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Flavonoids possess pharmaceutical potential due to their health-promoting activities. The complex structures of these products make extraction from plants difficult, and chemical synthesis is limited because of the use of many toxic solvents. Microbial production offers an alternate way to produce these compounds on an industrial scale in a more economical and environment-friendly manner. However, at present microbial production has been achieved only on a laboratory scale and improvements and scale-up of these processes remain challenging. Naringenin and pinocembrin, which are flavonoid scaffolds and precursors for most of the flavonoids, are the model molecules that are key to solving the current issues restricting industrial production of these chemicals. The emergence of systems metabolic engineering, which combines systems biology with synthetic biology and evolutionary engineering at the systems level, offers new perspectives on strain and process optimization. In this review, current challenges in large-scale fermentation processes involving flavonoid scaffolds and the strategies and tools of systems metabolic engineering used to overcome these challenges are summarized. This will offer insights into overcoming the limitations and challenges of large-scale microbial production of these important pharmaceutical compounds.
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Vitamin D status and risk of non-Hodgkin lymphoma: a meta-analysis.
Cancer Causes Control
PUBLISHED: 08-23-2014
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Non-Hodgkin lymphoma (NHL) is among the ten most frequent malignancies in Europe and USA. Results for vitamin D status and risk of NHL have been inconsistent.
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Clearance of serum solutes by hemofiltration in dogs with severe heat stroke.
Scand J Trauma Resusc Emerg Med
PUBLISHED: 08-22-2014
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We have previously reported that hemofiltration (HF) may be an effective additional means of treating heat stroke when rapid cooling is not effective.
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[A blind technique used in randomized controlled trials of treatment based on changes of syndromes].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 08-21-2014
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Treatment based on syndrome differentiation is an essential feature of traditional Chinese medical diagnosis. The interventions based on changes of syndrome types in randomized controlled trials are complicated, leading to the difficulty of blind method enforcement. This article described a double-blind method. It could be used in randomized controlled trials under the condition of different syndrome types and different medications. It numbered drugs in two stages, and in two phases to achieve double-blind. This method not only guaranteed investigators and subjects to be in blinded conditions, but also achieved using different medications for patients of different syndromes. It also caused no drug waste. It was scientific and feasible.
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Generation of a mouse model of T-cell lymphoma based on chronic LPS challenge and TGF-? signaling disruption.
Genes Cancer
PUBLISHED: 08-20-2014
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asymptomatic steatosis, alcoholic hepatitis and alcoholic cirrhosis, which substantially increase the risk for developing hepatocellular carcinoma. Transforming growth factor (TGF-?) signaling pathway is a major regulator in chronic liver diseases contributing to all liver disease progression from liver injury, inflammation and fibrosis to HCC. With the aim of generating a mouse model of alcoholic liver disease that would rapidly develop steatosis, inflammation as well as fibrosis, we formulated a regimen that combined chronic injections of low dose (2mg/kg) lipopolysaccharide (LPS) with Lieber DeCarli-based diet containing 6.7% ethanol feeding to mice with impaired TGF-? signaling through constitutive disruption of ?2-spectrin and/or Smad3. Unexpectedly, the mice treated with chronic low dose LPS and fed the alcohol-containing diet developed very aggressive T-cell lymphomas to which the TGF-? mutant mice succumbed more rapidly than the wild type mice. In contrast, their liver phenotype was mild as they only developed steatosis but not hepatitis or significant fibrosis. To our knowledge, this is the first report of a mouse model of aggressive T- cell lymphoma based on chronic challenge with low dose LPS and TGF-? disruption.
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Construction of corneal epithelium with human amniotic epithelial cells and repair of limbal deficiency in rabbit models.
Hum. Cell
PUBLISHED: 08-19-2014
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This study aims to evaluate the effect of a human amniotic epithelial cell (HAEC)-rabbit corneal stroma tissue-engineered cornea on ocular reconstruction in three different animal models. HAECs were isolated from human placenta, seeded onto rabbit corneal stroma. HAECs-rabbit corneal stroma tissue engineering cornea transplantation was examined in three distinct rabbit models: transplantation of cornea constructed (1) with lamellar corneal HAECs and rabbit corneal stroma, (2) with central corneal HAECs and rabbit corneal stroma, or (3) with full-thickness corneal HAECs and rabbit corneal stroma. In the tissue engineering corneal transplantation groups in all three models, the mean number of days to corneal epithelial healing was significantly shorter than that in the control group and the mean number of days to corneal neovascularization was significantly greater than in the control group. In addition, in the tissue engineering corneal transplantation groups in the central lamellar cornea model and the full-thickness corneal transplantation model neovascularization, corneal turbidity, and epithelial fluorescence were significantly less than in the control groups. HAECs can be induced to differentiate into corneal epithelial cells, which may be suitable for the reconstruction of the corneal epithelium in cases of limbal stem cell deficiency.
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A new synthetic ursolic acid derivative IUA with anti-tumor efficacy against osteosarcoma cells via inhibition of JNK signaling pathway.
Cell. Physiol. Biochem.
PUBLISHED: 08-18-2014
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Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and is characterized by frequent metastasis and resistance to chemotherapy. Because osteosarcoma cells are not highly susceptible to current chemotherapy drugs, new alternative strategies for the treatment of osteosarcoma are needed. This study was undertaken to investigate the inhibitory effects of a new synthetic ursolic acid derivative IUA on osteosarcoma cells and to explore its molecular mechanism. We also intended to identify new therapeutic candidates.
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Improving antimicrobial dosing in critically ill patients receiving continuous venovenous hemofiltration and the effect of pharmacist dosing adjustment.
Eur. J. Intern. Med.
PUBLISHED: 08-18-2014
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Appropriate antimicrobial dosing for patients receiving continuous venovenous hemofiltration (CVVH) is complex. Pharmacist participation in antimicrobial dosing adjustment for patients receiving CVVH may be advantageous.
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[Effects of bm47 deletion on viral replication and transcription of Bombyx mori nucleopolyhedrovirus].
Bing Du Xue Bao
PUBLISHED: 08-15-2014
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Bombyx mori nucleopolyhedrovirus (BmNPV) bm47 gene is found in all sequenced lepidopteran nucleopolyhedroviruses (NPVs). It is one of the core genes of NPVs. However, the role of bm47 in the biological cycle of NPV remains unknown. In this study, the Red recombination system was used to knock out bm47 from BmNPV to construct bm47-ko-Bacmid in E. coli BW25113 system. Then bm47 gene was introduced back to the viral genome using the Bac-to-Bac system to create the repair virus bm47-re-Bacmid. TCID50 assay and real-time PCR (qPCR) were used to evaluate the effects of bm47 deletion on viral DNA replication, gene transcription, and protein expression. qPCR results showed that bm47 knock-out had no significant effect on viral DNA replication. However, the qPCR results showed that bm47-ko-Bacmid significantly decreased the transcription levels of early gene lef-3, late gene vp39, and very late gene p10 at 48 h and 72 h after viral transfection of BmN cells (P < 0.05). This work will provide a foundation for further studies on the biological function of BmNPV bm47 in viral replication and transcription.
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MiR-605 represses PSMD10/Gankyrin and inhibits intrahepatic cholangiocarcinoma cell progression.
FEBS Lett.
PUBLISHED: 08-14-2014
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The aberrant expression of PSMD10 has important functions in various malignancies. This study showed that PSMD10 was highly expressed and inversely correlated with the expression of miR-605 in intrahepatic cholangiocarcinoma (ICC) specimens. MiR-605 directly targeted and repressed PSMD10 expression. In addition, over-expression of miR-605 inhibited ICC cell progression both in vitro and in vivo. This effect of miR-605 on ICC cells was similar to that of PSMD10 knock-down by RNAi. Moreover, restoration of PSMD10 could reverse the phenotypic alteration caused by miR-605 in ICC cells. These results suggest a new therapeutic strategy in ICC by restoring miR-605, which is regulated by p53.
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Volatilization of arsenic from polluted soil by Pseudomonas putida engineered for expression of the arsM Arsenic(III) S-adenosine methyltransferase gene.
Environ. Sci. Technol.
PUBLISHED: 08-14-2014
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Even though arsenic is one of the most widespread environmental carcinogens, methods of remediation are still limited. In this report we demonstrate that a strain of Pseudomonas putida KT2440 endowed with chromosomal expression of the arsM gene encoding the As(III) S-adenosylmethionine (SAM) methyltransfase from Rhodopseudomonas palustris to remove arsenic from contaminated soil. We genetically engineered the P. putida KT2440 with stable expression of an arsM-gfp fusion gene (GE P. putida), which was inserted into the bacterial chromosome. GE P. putida showed high arsenic methylation and volatilization activity. When exposed to 25 ?M arsenite or arsenate overnight, most inorganic arsenic was methylated to the less toxic methylated arsenicals methylarsenate (MAs(V)), dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAs(V)O). Of total added arsenic, the species were about 62 ± 2.2% DMAs(V), 25 ± 1.4% MAs(V) and 10 ± 1.2% TMAs(V)O. Volatilized arsenicals were trapped, and the predominant species were dimethylarsine (Me2AsH) (21 ± 1.0%) and trimethylarsine (TMAs(III)) (10 ± 1.2%). At later times, more DMAs(V) and volatile species were produced. Volatilization of Me2AsH and TMAs(III) from contaminated soil is thus possible with this genetically engineered bacterium and could be instrumental as an agent for reducing the inorganic arsenic content of soil and agricultural products.
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Fluorescence-guided resection of high-grade gliomas: A systematic review and meta-analysis.
Photodiagnosis Photodyn Ther
PUBLISHED: 08-12-2014
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The present systematic review and meta-analysis was to analysis of the advantages of intraoperative fluorescence-guided resection of high-grade gliomas.
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Expression of Neural Wiskott-Aldrich Syndrome Protein in Clear Cell Renal Cell Carcinoma and Its Correlation with Clinicopathological Features.
Urol. Int.
PUBLISHED: 08-07-2014
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Introduction: Neural Wiskott-Aldrich syndrome protein (N-WASP) expression is associated with tumor cell invasion and migration. However, its expression status in clear cell renal cell carcinoma (CCRCC) remains unclear. We examined the level of N-WASP in CCRCC and its association with clinicopathological features characteristic. Materials and Methods: 73 CCRCC patients who underwent radical nephrectomy or partial nephrectomy were enrolled. Immunohistochemical staining for N-WASP was performed on tissue microarrays constructed from tumor and para-tumor tissue obtained from these patients. The difference in N-WASP expression between tumor tissue and adjacent normal renal tissue was examined. Correlations between N-WASP expression in the tumor and clinicopathological parameters were analyzed and the relationship between N-WASP expression and overall survival also assessed. Uni- and multivariate survival analyses were performed. Results: N-WASP expression was significantly reduced in tumor tissues and was significantly related to the histological grade of CCRCC. A higher level of N-WASP expression in the tumor was associated with relatively poor survival in CCRCC patients. The level of N-WASP expression, age at time of surgery, and histological grade were all responsible for clinical outcome in CCRCC patients. N-WASP was an independent predictor for overall survival. Conclusions: N-WASP was downregulated in CCRCC and could serve as a prognostic biomarker for predicting clinical outcome of CCRCC. © 2014 S. Karger AG, Basel.
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The MBD4 Gene Plays an Important Role in Porcine Adipocyte Differentiation.
Cell. Physiol. Biochem.
PUBLISHED: 08-06-2014
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MBD4 (methyl-CpG binding domain protein 4) is an important G: T glycosylase that can identify T-G mismatches. It plays a role in active demethylation through base excision repair. Overexpression of MBD4 gene can cause the demethylation of numerous genes, and the remethylation of MBD4-associated genes can occur when the MBD4 gene is knocked out. To date, the functions and regulatory mechanisms of the MBD4 gene in the differentiation of porcine preadipocytes have not been clearly established.
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Association between Vitamin D level and viral load or fibrosis stage in chronic hepatitis B patients from Southern China.
J. Gastroenterol. Hepatol.
PUBLISHED: 08-05-2014
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The role vitamin D playing in patients with chronic hepatitis C has been intensively studied. However, studies on the potential interaction between vitamin D level and chronic hepatitis B are still limited. This study aimed to explore whether any association existed between serum vitamin D level and liver histology or virological parameters in patients with chronic hepatitis B infection in Southern China.
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Technical evaluation of Virtual Touch™ tissue quantification and elastography in benign and malignant breast tumors.
Exp Ther Med
PUBLISHED: 08-04-2014
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The aim of this study was to investigate the diagnostic value of the Virtual Touch™ tissue quantification (VTQ) and elastosonography technologies in benign and malignant breast tumors. Routine preoperative ultrasound, elastosonography and VTQ examinations were performed on 86 patients with breast lesions. The elastosonography score and VTQ speed grouping of each lesion were measured and compared with the pathological findings. The difference in the elastosonography score between the benign and malignant breast tumors was statistically significant (P<0.05). The detection rate for an elastosonography score of 1-3 points in benign tumors was 68.09% and that for an elastosonography score of 4-5 points in malignant tumors was 82.05%. The difference in VTQ speed values between the benign and malignant tumors was also statistically significant (P<0.05). In addition, the diagnostic accuracy of conventional ultrasound, elastosonography, VTQ technology and the combined methods showed statistically significant differences (P<0.05). The use of the three technologies in combination significantly improved the diagnostic accuracy to 91.86%. In conclusion, the combination of conventional ultrasound, elastosonography and VTQ technology can significantly improve accuracy in the diagnosis of breast cancer.
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High-Level Extracellular Production of Glucose Oxidase by Recombinant Pichia Pastoris Using a Combined Strategy.
Appl. Biochem. Biotechnol.
PUBLISHED: 07-31-2014
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In this work, a combined strategy was developed to improve the production of glucose oxidase (GOD) (EC 1.1.3.4) in Pichia pastoris. One of the main challenges facing protein production by the high-density fermentation of P. pastoris is the high demand for oxygen. Another challenge is how to balance a reduction in oxygen consumption and its effects on protein production. Herein, a combined strategy involving mannitol co-feeding, two-stage methanol induction, and the co-expression of the transcriptional activator general control non-derepressible 4 (GCN4) from P. pastoris was used. A two-stage, co-feeding strategy, based on a mannitol/methanol mixture in a 3-L fermentor was used to enhance cell viability and protein production. This resulted in an increased GOD yield of 1208.2 U/mL compared with a control strain (427.6 U/mL). An increase in the copy number of the GCN4 gene enhanced the GOD yield (1634.7 U/mL) by 2.8-fold and the protein concentration (19.55 g/L) by 1.58-fold compared with the control (7.59 g/L). This strategy illustrates a way to overcome the high oxygen requirement during high-density fermentation of P. pastoris and balances the reduction of oxygen consumption and protein production. Moreover, the series of strategies presented in this work provide valuable and novel information for the industrial production of GOD.
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MAN3 gene regulates cadmium tolerance through the glutathione-dependent pathway in Arabidopsis thaliana.
New Phytol.
PUBLISHED: 07-24-2014
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Pollution of soil by the heavy metal cadmium (Cd) is a global environmental problem. The glutathione (GSH)-dependent phytochelatin (PC) synthesis pathway is one of the most important mechanisms contributing to Cd accumulation and tolerance. However, the regulation of this pathway is poorly understood. Here, we identified an Arabidopsis thaliana cadmium-tolerant dominant mutant xcd1-D (XVE system-induced cadmium-tolerance 1) and cloned XCD1 gene (previously called MAN3), which encodes an endo-?-mannanase. Overexpression of MAN3 led to enhanced Cd accumulation and tolerance, whereas loss-of-function of MAN3 resulted in decreased Cd accumulation and tolerance. In the presence of estradiol, enhanced Cd accumulation and tolerance in xcd1-D was associated with GSH-dependent, Cd-activated synthesis of PCs, which was correlated with coordinated activation of gene expression. Cd stress-induced expression of MAN3 and the consequently increased mannanase activity, led to increased mannose content in cell walls. Moreover, mannose treatment not only rescued the Cd-sensitive phenotype of the xcd1-2 mutant, but also improved the Cd tolerance of wild-type plants. Significantly, this mannose-mediated Cd accumulation and tolerance is dependent on GSH-dependent PC concentrations via coordinated control of expression of genes involved in PC synthesis. Our results suggest that MAN3 regulates the GSH-dependent PC synthesis pathway that contributes to Cd accumulation and tolerance in A. thaliana by coordinated control of gene expression.
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Enhanced production of L-sorbose from D-sorbitol by improving the mRNA abundance of sorbitol dehydrogenase in Gluconobacter oxydans WSH-003.
Microb. Cell Fact.
PUBLISHED: 07-19-2014
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BackgroundProduction of L-sorbose from D-sorbitol by Gluconobacter oxydans is the first step to produce L-ascorbic acid on industrial scale. The sldhAB gene, which encodes the sorbitol dehydrogenase (SLDH), was overexpressed in an industrial strain G. oxydans WSH-003 with a strong promoter, P tufB . To enhance the mRNA abundance, a series of artificial poly(A/T) tails were added to the 3¿-terminal of sldhAB gene. Besides, their role in sldhAB overexpression and their subsequent effects on L-sorbose production were investigated.ResultsThe mRNA abundance of the sldhAB gene could be enhanced in G. oxydans by suitable poly(A/T) tails. By self-overexpressing the sldhAB gene in G. oxydans WSH-003 with an optimal poly(A/T) tail under the constitutive promoter P tufB , the titer and the productivity of L-sorbose were enhanced by 36.3% and 25.0%, respectively, in a 1-L fermenter. Immobilization of G. oxydans-sldhAB6 cells further improved the L-sorbose titer by 33.7% after 20 days of semi-continuous fed-batch fermentation.ConclusionsThe artificial poly(A/T) tails could significantly enhance the mRNA abundance of the sldhAB. Immobilized G. oxydans-sldhAB6 cells could further enlarge the positive effect caused by enhanced mRNA abundance of the sldhAB.
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Shape-Reprogrammable Polymers: Encoding, Erasing, and Re-encoding.
Adv. Mater. Weinheim
PUBLISHED: 06-30-2014
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Shape-reprogramming in a polymer is demonstrated, where prescribed 3D geometric information can be encoded, decoded, erased, and re-encoded. In essence, the shape-reprogrammable polymer (SRP) acts as computer hardware that can be reformatted and reprogrammed repeatedly. Such SRPs have the potential to be repurposed directly without going through material disposal and recycling.
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Understanding of how Propionibacterium acidipropionici respond to propionic acid stress at the level of proteomics.
Sci Rep
PUBLISHED: 06-27-2014
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Propionic acid (PA) is an important platform chemical in the food, agriculture, and pharmaceutical industries and is mainly biosynthesized by propionibacteria. Acid tolerance in PA-producing strains is crucial. In previous work, we investigated the acid tolerance mechanism of Propionibacterium acidipropionici at microenvironmental levels by analyzing physiological changes in the parental strain and three PA-tolerant mutants obtained by genome shuffling. However, the molecular mechanism of PA tolerance in P. acidipropionici remained unclear. Here, we performed a comparative proteomics study of P. acidipropionici CGMCC 1.2230 and the acid-tolerant mutant P. acidipropionici WSH1105; MALDI-TOF/MS identified 24 proteins that significantly differed between the parental and shuffled strains. The differentially expressed proteins were mainly categorized as key components of crucial biological processes and the acid stress response. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to confirm differential expression of nine key proteins. Overexpression of the secretory protein glyceraldehyde-3-phosphate dehydrogenase and ATP synthase subunit ? in Escherichia coli BL21 improved PA and acetic acid tolerance; overexpression of NADH dehydrogenase and methylmalonyl-CoA epimerase improved PA tolerance. These results provide new insights into the acid tolerance of P. acidipropionici and will facilitate the development of PA production through fermentation by propionibacteria.
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10058-F4, a c-Myc inhibitor, markedly increases valproic acid-induced cell death in Jurkat and CCRF-CEM T-lymphoblastic leukemia cells.
Oncol Lett
PUBLISHED: 06-24-2014
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Adult T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis. Although it has been found that activation of Notch1 signaling occurs in >50% T-ALL patients, ?-secretase inhibitors that target Notch1 signaling are of limited efficacy. However, c-Myc is an important direct target of Notch1 and, thus, c-Myc is another potential therapeutic target for T-ALL. Valproic acid (VPA), a histone deacetylase inhibitor, has been reported to treat various hematological malignancies. In the present study, we showed that c-Myc expression, at a transcriptional level, was dose-dependently downregulated in VPA-induced growth inhibition in T-ALL cell lines, Jurkat and CCRF-CEM cells. 10058-F4, a small molecule c-Myc inhibitor, could increase the downregulation of c-Myc and markedly increase the growth inhibition and cell death induced by VPA in Jurkat and CCRF-CEM cells, which was accompanied by obvious cleavage of capase-3. Z-VAD-FMK, a caspase inhibitor, partially prevented the anti-leukemic effect. The results of the present study suggest that c-Myc inhibitors increase cell death induced by VPA in a caspase-dependent and -independent manner, and their combination could be a potent therapeutic strategy for adult T-ALL patients.
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An innovative, multi-arm, complete phase 1b study of the novel anti-cancer agent tasisulam in patients with advanced solid tumors.
Invest New Drugs
PUBLISHED: 06-13-2014
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Background This phase Ib study used a parallel, multi-arm design to examine tasisulam-sodium (hereafter tasisulam), a drug with complex pharmacology, combined with standard chemotherapies in patients with advanced solid tumors, with the ultimate goal of accelerating drug development. Methods Patients received escalating doses of tasisulam (3?+?3 schema; target Cmax 300-400 ?g/mL) every 28 days plus 1,000 mg/m(2) gemcitabine HCl (days 1 and 15), 60 mg/m(2) docetaxel, 200 mg/m(2)/day temozolomide, 75 mg/m(2) cisplatin, or 150 mg/day erlotinib. Following dose-escalation, patients were enrolled into specific tumor subtype arms, chosen based on the established activity of the standard agent. Because tasisulam is highly albumin-bound, patients in the tumor-specific confirmation arms were dosed targeting specific albumin-corrected exposure ranges (AUCalb) identified during dose-escalation (3,500 h*?g/mL [75th percentile] for docetaxel, temozolomide, and cisplatin; 4,000 h*?g/mL for gemcitabine and erlotinib). Results A total of 234 patients were enrolled. The safety profile of tasisulam with standard chemotherapies was sufficient to allow enrollment into the dose-confirmation phase in all arms. The primary dose-limiting toxicities were hematologic (thrombocytopenia and neutropenia). The most common grade ?3 drug-related treatment-emergent adverse event was neutropenia, with the highest incidence in the docetaxel arm. Conclusions The multi-arm design allowed the efficient determination of the maximum tolerated dose of tasisulam across multiple combinations, and a preliminary characterization of pharmacokinetics, safety, and potential efficacy. Although enrollment into all planned groups was not completed due to termination of compound development, these data support the feasibility of this approach for accelerated cancer drug development, even for drugs with complex pharmacology.
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Effect of Fibulin-5 on cell proliferation and invasion in human gastric cancer patients.
Asian Pac J Trop Med
PUBLISHED: 06-10-2014
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To explore the effect of Fibulin-5 expression on cell proliferation and invasion in human gastric cancer patients.
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Overexpression of sorcin in multidrug-resistant human breast cancer.
Oncol Lett
PUBLISHED: 05-14-2014
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Sorcin is a soluble resistance-related calcium-binding protein, which is expressed in normal mammalian tissues, such as the liver, lungs and heart. It has been observed to be elevated in a number of cancer types, including colorectal, gastric and breast cancer. Its upregulation is usually associated with the development of chemotherapeutic drug resistance. The aim of this study was to evaluate the sorcin expression levels in human serum samples of breast cancer subjects at various stages, and subsequently compare the outcome of neoadjuvant chemotherapy when the sorcin levels fluctuated. In total, 50 subjects were recruited from patients who were admitted to Yantai Yuhunagding Hospital (Yantai, China) and diagnosed with breast cancer. Blood samples prior to and following chemotherapy were assessed using two-dimensional gel electrophoresis (2-DE) and western blot analysis. The 2-DE analysis of the serum samples revealed that sorcin was upregulated in six out of 29 neoadjuvant chemotherapy (NAC)-sensitive patients and, in those who developed multidrug resistance, sorcin was upregulated in 15 out of 21 patients (P<0.01). The differential expression levels of sorcin were confirmed by western blot and immunohistochemical analysis. In conclusion, sorcin expression in the human serum of breast cancer patients who are resistant to NAC was elevated when compared with that of NAC-sensitive patients.
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Priapism as the initial symptom of primary penile lymphoma: A case report.
Oncol Lett
PUBLISHED: 05-06-2014
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Primary penile lymphoma presenting with priapism as the initial symptom is extremely rare. In total, <10 cases have been previously reported. The diagnosis can be difficult and patients often develop metastasis. The current study reports the case of a 48-year-old male, who presented with a one-month history of painless priapism. On admission to Yantai Yuhuangding Hospital Affiliated to Qingdao University (Yantai, China), examination revealed an erect penis, enlarged lymph nodes in the bilateral inguinal and swelling in the thighs. A biopsy was taken from the right inguinal lymph node and the pathological diagnosis confirmed a diffuse large B-cell type of non-Hodgkin's lymphoma, while an enhanced computed tomography scan of the chest revealed evidence of the invasion of malignant lymphoma cells. Priapism disappeared two days following the completion of the first cycle of chemotherapy with the E-CHOP regimen (cyclophosphamide, vincristine, prednisone, epirubicin and etoposide); however, evidence of brain metastases was observed one month later, which was confirmed by magnetic resonance imaging. The patient received cranial radiotheraphy and systemic treatment for cerebral edema. The patient did not respond well to treatment and succumbed to the disease three months following the initial diagnosis of lymphoma. Lymphoma may be difficult to diagnose, depending on the initial symptoms; therefore, the patient history must be carefully assessed so as to determine an early diagnosis and prevent metastasis, thus improving the prognostic outcome.
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Altered cortical thickness following prenatal sodium valproate exposure.
Ann Clin Transl Neurol
PUBLISHED: 05-03-2014
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Prenatal exposure to sodium valproate (VPA) is associated with neurodevelopmental impairments. Cortical thickness was measured in 16 children exposed prenatally to VPA and 16 controls. We found increased left inferior frontal gyrus (IFG; BA45) and left pericalcarine sulcus (BA18) thickness, an association between VPA dose and right IFG thickness, and a close relationship between verbal skills and left IFG thickness. A significant interaction between group and hemispheric IFG thickness showed absence of the normal asymmetry in the IFG region of VPA-exposed children. These data provide preliminary insights into the putative neural basis of difficulties experienced by some VPA-exposed children.
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Molecular engineering of secretory machinery components for high-level secretion of proteins in Bacillus species.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 05-03-2014
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Secretory expression of valuable enzymes by Bacillus subtilis and its related species has attracted intensive work over the past three decades. Although many proteins have been expressed and secreted, the titers of some recombinant enzymes are still low to meet the needs of practical applications. Signal peptides that located at the N-terminal of nascent peptide chains play crucial roles in the secretion process. In this mini-review, we summarize recent progress in secretory expression of recombinant proteins in Bacillus species. In particular, we highlighted and discussed the advances in molecular engineering of secretory machinery components, construction of signal sequence libraries and identification of functional signal peptides with high-throughput screening strategy. The prospects of future research are also proposed.
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Effects of unidentified renal insufficiency on the safety and efficacy of chemotherapy for metastatic colorectal cancer patients: a prospective, observational study.
Support Care Cancer
PUBLISHED: 04-11-2014
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This is a single-center, prospective, observational study aiming to determine the effects of unidentified renal insufficiency (URI) on the safety and efficacy of chemotherapy for metastatic colorectal cancer (mCRC) patients.
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Identification of membrane proteins associated with phenylpropanoid tolerance and transport in Escherichia coli BL21.
J Proteomics
PUBLISHED: 04-08-2014
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Phenylpropanoids are phytochemicals produced by some plants and possess a wide variety of biological activities. These compounds exist in plants in low amounts. Production of them in genetically engineered microorganisms has many advantages. A majority of functional phenylpropanoids are toxic to microbial hosts. Export of these compounds may relieve the cellular toxicity and increase the yield. However, proteins and mechanisms involved in phenylpropanoids transport and tolerance remain poorly understood. In this study, 16 membrane proteins that were differentially expressed in Escherichia coli in response to three typical phenylpropanoids (resveratrol, naringenin and rutin) were identified using a membrane proteomics approach. These proteins included outer membrane proteins OmpA, OmpF, OmpW, FadL, TolC, LamB, and YaeT, peripheral membrane proteins AtpD, AtpH, YgaU, OppA, MalK, and MalE, and cytoplasmic membrane proteins OppD, PotG, and ManX. Functions of these proteins were determined by using gene overexpression and silencing. The results suggest that OmpA and FadL may play important roles in the transmembrane export of phenylpropanoids in E. coli. LamB, MalE, MalK and ManX may participate in phenylpropanoid uptake. The role of YgaU in enhancing the tolerance to phenylpropanoids remains to be determined. These results may assist the engineering of microorganisms with enhanced phenylpropanoid producing capabilities.
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CSN6 drives carcinogenesis by positively regulating Myc stability.
Nat Commun
PUBLISHED: 02-27-2014
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Cullin-RING ubiquitin ligases (CRLs) are critical in ubiquitinating Myc, while COP9 signalosome (CSN) controls neddylation of Cullin in CRL. The mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is unclear. Here we show that Myc is a target of the CSN subunit 6 (CSN6)-Cullin signalling axis and that CSN6 is a positive regulator of Myc. CSN6 enhanced neddylation of Cullin-1 and facilitated autoubiquitination/degradation of Fbxw7, a component of CRL involved in Myc ubiquitination, thereby stabilizing Myc. Csn6 haplo-insufficiency decreased Cullin-1 neddylation but increased Fbxw7 stability to compromise Myc stability and activity in an E?-Myc mouse model, resulting in decelerated lymphomagenesis. We found that CSN6 overexpression, which leads to aberrant expression of Myc target genes, is frequent in human cancers. Together, these results define a mechanism for the regulation of Myc stability through the CSN-Cullin-Fbxw7 axis and provide insights into the correlation of CSN6 overexpression with Myc stabilization/activation during tumorigenesis.
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Novel fermentation processes for manufacturing plant natural products.
Curr. Opin. Biotechnol.
PUBLISHED: 02-04-2014
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Microbial production of plant natural products (PNPs), such as terpenoids, flavonoids from renewable carbohydrate feedstocks offers sustainable and economically attractive alternatives to their petroleum-based production. Rapid development of metabolic engineering and synthetic biology of microorganisms shows many advantages to replace the current extraction of these useful high price chemicals from plants. Although few of them were actually applied on a large scale for PNPs production, continuous research on these high-price chemicals and the rapid growing global market of them, show the promising future for the production of these PNPs by microorganisms with a more economic and environmental friendly way. Introduction of novel pathways and optimization of the native cellular processes by metabolic engineering of microorganisms for PNPs production are rapidly expanding its range of cell-factory applications. Here we review recent progress in metabolic engineering of microorganisms for the production of PNPs. Besides, factors restricting the yield improvement and application of lab-scale achievements to industrial applications have also been discussed.
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A graphene quantum dot-based method for the highly sensitive and selective fluorescence turn on detection of biothiols.
Talanta
PUBLISHED: 01-10-2014
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A facile assay method for the highly sensitive and selective sensing of biothiols based on graphene quantum dots (GQDs) has been developed. GQDs emitted strong blue fluorescence in an aqueous buffer solution. It was observed that mercury(II) ions could efficiently bind and quench the fluorescence of the GQDs. When a biothiol compound (glutathione, cysteine, or homocysteine) was added to the assay mixture of GQDs and mercury(II), it bound to mercury(II) ions. Hg(2+)-GQD complex dissociated, and a fluorescence turn-on signal was detected. The emission intensity changes of the GQDs could be directly related to the amount of biothiol added to the assay solution. The assay is highly sensitive, the limits of detection (LOD) for GSH, Cys and Hcy were 5 nM, 2.5 nM and 5 nM, respectively. The assay is also highly selective, a number of amino acids and proteins were tested, and little interference was observed. In addition, GSH standard recovery in serum samples was also demonstrated. We envision that our assay method could facilitate the biothiol quantification related biological and biomedical research.
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Expression of mineralocorticoid and glucocorticoid receptors in preautonomic neurons of the rat paraventricular nucleus.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 01-02-2014
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Activation of mineralocorticoid receptors (MR) of the hypothalamic paraventricular nucleus (PVN) increases sympathetic excitation. To determine whether MR and glucocorticoid receptors (GR) are expressed in preautonomic neurons of the PVN and how they relate to endogenous aldosterone levels in healthy rats, retrograde tracer was injected into the intermediolateral cell column at T4 to identify preautonomic neurons in the PVN. Expression of MR, GR, 11-? hydroxysteroid dehydrogenase1 and 2 (11?-HSD1, 2), and hexose-6-phosphate dehydrogenase (H6PD) required for 11?-HSD1 reductase activity was assessed by immunohistochemistry. RT-PCR and Western blot analysis were used to determine MR gene and protein expression. Most preautonomic neurons were in the caudal mediocellular region of PVN, and most expressed MR; none expressed GR. 11?-HSD1, but not 11?-HSD2 nor H6PD immunoreactivity, was detected in the PVN. In rats with chronic low or high sodium intakes, the low-sodium diet was associated with significantly higher plasma aldosterone, MR mRNA and protein expression, and c-Fos immunoreactivity within labeled preautonomic neurons. Plasma corticosterone and sodium and expression of tonicity-responsive enhancer binding protein in the PVN did not differ between groups, suggesting osmotic adaptation to the altered sodium intake. These results suggest that MR within preautonomic neurons in the PVN directly participate in the regulation of sympathetic nervous system drive, and aldosterone may be a relevant ligand for MR in preautonomic neurons of the PVN under physiological conditions. Dehydrogenase activity of 11?-HSD1 occurs in the absence of H6PD, which regenerates NADP(+) from NADPH and may increase MR gene expression under physiological conditions.
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P2Y6 Receptor Potentiates Pro-Inflammatory Responses in Macrophages and Exhibits Differential Roles in Atherosclerotic Lesion Development.
PLoS ONE
PUBLISHED: 01-01-2014
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P2Y6, a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y6 deficiency on atherosclerosis.
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The Endogenous Nitric Oxide Mediates Selenium-Induced Phytotoxicity by Promoting ROS Generation in Brassica rapa.
PLoS ONE
PUBLISHED: 01-01-2014
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Selenium (Se) is suggested as an emerging pollutant in agricultural environment because of the increasing anthropogenic release of Se, which in turn results in phytotoxicity. The most common consequence of Se-induced toxicity in plants is oxidative injury, but how Se induces reactive oxygen species (ROS) burst remains unclear. In this work, histofluorescent staining was applied to monitor the dynamics of ROS and nitric oxide (NO) in the root of Brassica rapa under Se(IV) stress. Se(IV)-induced faster accumulation of NO than ROS. Both NO and ROS accumulation were positively correlated with Se(IV)-induced inhibition of root growth. The NO accumulation was nitrate reductase (NR)- and nitric oxide synthase (NOS)-dependent while ROS accumulation was NADPH oxidase-dependent. The removal of NO by NR inhibitor, NOS inhibitor, and NO scavenger could alleviate Se(IV)-induced expression of Br_Rbohs coding for NADPH oxidase and the following ROS accumulation in roots, which further resulted in the amelioration of Se(IV)-induced oxidative injury and growth inhibition. Thus, we proposed that the endogenous NO played a toxic role in B. rapa under Se(IV) stress by triggering ROS burst. Such findings can be used to evaluate the toxic effects of Se contamination on crop plants.
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Selenium Inhibits Root Elongation by Repressing the Generation of Endogenous Hydrogen Sulfide in Brassica rapa.
PLoS ONE
PUBLISHED: 01-01-2014
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Selenium (Se) has been becoming an emerging pollutant causing severe phytotoxicity, which the biochemical mechanism is rarely known. Although hydrogen sulfide (H2S) has been suggested as an important exogenous regulator modulating plant physiological adaptions in response to heavy metal stress, whether and how the endogenous H2S regulates Se-induce phytotoxicity remains unclear. In this work, a self-developed specific fluorescent probe (WSP-1) was applied to track endogenous H2S in situ in the roots of Brassica rapa under Se(IV) stress. Se(IV)-induced root growth stunt was closely correlated with the inhibition of endogenous H2S generation in root tips. Se(IV) stress dampened the expression of most LCD and DCD homologues in the roots of B. rapa. By using various specific fluorescent probes for bio-imaging root tips in situ, we found that the increase in endogenous H2S by the application of H2S donor NaHS could significantly alleviate Se(IV)-induced reactive oxygen species (ROS) over-accumulation, oxidative impairment, and cell death in root tips, which further resulted in the recovery of root growth under Se(IV) stress. However, dampening the endogenous H2S could block the alleviated effect of NaHS on Se(IV)-induced phytotoxicity. Finally, the increase in endogenous H2S resulted in the enhancement of glutathione (GSH) in Se(IV)-treated roots, which may share the similar molecular mechanism for the dominant role of H2S in removing ROS by activating GSH biosynthesis in mammals. Altogether, these data provide the first direct evidences confirming the pivotal role of endogenous H2S in modulating Se(IV)-induced phytotoxicity in roots.
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