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Find video protocols related to scientific articles indexed in Pubmed.
Penicibilaenes A and B, Sesquiterpenes with a Tricyclo[6.3.1.0(1,5)]dodecane Skeleton from the Marine Isolate of Penicillium bilaiae MA-267.
Org. Lett.
PUBLISHED: 11-20-2014
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Penicibilaenes A (1) and B (2), two sesquiterpenes possessing a tricyclo[6.3.1.0(1,5)]dodecane skeleton, were characterized from Penicillium bilaiae MA-267, a fungus obtained from the rhizospheric soil of the mangrove plant Lumnitzera racemosa. The lack of some key COSY and NOESY correlations made the structure elucidation of compound 1 difficult, which was solved by a X-ray crystallographic study. Compounds 1 and 2 exhibited selective activity against the plant pathogenic fungus Colletotrichum gloeosporioides (MIC = 1.0 and 0.125 ?g/mL, respectively).
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Delayed rearterialization unlikely leads to non-anastomotic stricture but causes temporary injury on bile duct after liver transplantation.
Transpl. Int.
PUBLISHED: 11-20-2014
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Non-anastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure.
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Silicon microring modulator for 40 Gb/s NRZ-OOK metro networks in O-band.
Opt Express
PUBLISHED: 11-18-2014
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A microring-based silicon modulator operating at 40 Gb/s near 1310 nm is demonstrated for the first time to our knowledge. NRZ-OOK signals at 40 Gb/s with 6.2 dB extinction ratio are observed by applying a 4.8 Vpp driving voltage and biasing the modulator at 7 dB insertion loss point. The energy efficiency is 115 fJ/bit. The transmission performance of 40 Gb/s NRZ-OOK through 40 km of standard single mode fiber without dispersion compensation is also investigated. We show that the link suffers negligible dispersion penalty. This makes the modulator a potential candidate for metro network applications.
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Mechanical Circulatory Support of a Univentricular Fontan Circulation with a Continuous Axial-Flow Pump in a Piglet Model.
ASAIO J.
PUBLISHED: 11-15-2014
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Despite the significant contribution of the Fontan procedure to the therapy of complex congenital heart diseases, many patients progress to failure of their Fontan circulation. The use of ventricular assist devices (VADs) to provide circulatory support to these patients remains challenging. In the present study, a continuous axial-flow pump was used to support a univentricular Fontan circulation. A modified Fontan circulation (atrio-pulmonary connection) was constructed in 6 Yorkshire piglets (8-14?kg). A Dacron conduit (12 mm) with 2 branches was constructed to serve as a complete atrio-pulmonary connection without the use of cardiopulmonary bypass. The Impella pump was inserted into the conduit through an additional PTFE graft in 5 animals. Hemodynamic data was collected for 6 hours under the supported Fontan circulation. The control animal died after initiating the Fontan circulation independent of resuscitation. Four pump supported animals remained hemodynamically stable for 6 hours with pump speeds between 18,000 rpm to 22,000 rpm (P1-P3). Oxygen saturation was maintained between 95-100%. Normal organ perfusion was illustrated by blood gas analysis and biochemical assays. A continuous axial-flow pump can be used for temporal circulatory support to the failing Fontan circulation as "bridge" to heart transplantation or recovery.
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Role of Serotonin in MODS: Deficiency of Serotonin Protects Against Zymosan-induced Multiple Organ Failure in Mice.
Shock
PUBLISHED: 11-14-2014
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Zymosan-induced multiple organ dysfunction syndrome (MODS) is a multi-factorial pathology that involves the deterioration of function in several organs. 5-hydroxytryptamine (5-HT) is a small monoamine molecule that is primarily known for its role as a neurotransmitter. Previous studies have shown that 5-HT could serve as an important inflammatory mediator in the peripheral immune system. In the present study, we investigated the effect of 5-HT on the development of non-septic shock caused by zymosan in mice. Tryptophan Hydroxylase 1 knockout mice (TPH1-/-, leading to the absence of 5-HT), TPH1-/- plus 5-Hydroxytryptophan (5-HTP, precursor of 5-HT) treatment mice, wild-type (TPH1+/+) mice, and wild-type plus p-chlorophenylalanine (PCPA, TPH1 inhibitor) treatment mice received zymosan intraperitoneally at a dose of 500 mg/kg. Organ failure and systemic inflammation in the mice were assessed 18 hours after the administration of zymosan. Deficiency of 5-HT caused a significant reduction of the (1) peritoneal exudate formation, (2) neutrophil infiltration, (3) multiple organ dysfunction syndrome, (4) nitrosative stress and (5) cytokine formation. In addition, at the end of the observation period (7 days), deficiency of 5-HT in the mice was shown to be able to alleviate the severe illness characterized as a systemic toxicity, significant loss of body weight and high mortality caused by the zymosan. In conclusion, the lack of 5-HT by genetic knockout or by pharmacologic inhibition of the TPH1 enzyme significantly attenuated zymosan-induced MODS.
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Vertical segregation in the self-assembly of nanoparticles at the liquid/air interface.
Nanoscale
PUBLISHED: 11-06-2014
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Vertical segregation was induced by the size-dependent charge neutralization during the one-step interfacial self-assembly of colloidal gold nanoparticles with bimodal size distribution. This self-assembly approach also can assemble particles with tunable compositions into layered films.
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Intra-arterial delivery of human bone marrow mesenchymal stem cells is a safe and effective way to treat cerebral ischemia in rats.
Cell Transplant
PUBLISHED: 11-06-2014
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Cerebral ischemic stroke is a very common condition that can cause death and disability. Studies have confirmed that stem cells have therapeutic effects if administered after stroke. There is still a great deal of debate regarding the best route for cell transplantation. Intravascular delivery is the most commonly used one. In this study, the therapeutic effects of bone marrow stem cells (BMSCs) delivered by intra-arterial (IA) and intravenous (IV) injection in a rat transient middle cerebral artery occlusion model (MCAO) are compared. Histological analysis demonstrated that the IA route bypasses the pulmonary system and directs the cells to the ischemic parts of the brain more efficiently. The BMSCs delivered via the IA route promoted angiogenesis and improved functional recovery. The cerebral blood flow (CBF) of the rats was monitored during the IA injection process. No reduction in CBF or microstrokes was detected. Brain perfusion and metabolism, as evaluated by SPECT and PET, were better in rats treated with cells delivered via IA. Results showed that the IA route is a safe and effective way to transplant hBMSCs.This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
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Laser-assisted generation of human induced pluripotent stem cells.
Curr Protoc Stem Cell Biol
PUBLISHED: 11-05-2014
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This unit describes a procedure for generating human induced pluripotent stem cells (hiPSCs) using the Laser-Enabled Analysis and Processing (LEAP®) system, which combines high-throughput cell imaging with laser-mediated cell manipulation. Use of this system should not only improve the quality and uniformity of hiPSCs produced, but ultimately enable a more rapid, efficient, high-throughput, and automated production process. © 2014 by John Wiley & Sons, Inc.
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Designing a Cu(II)-ArCu(II)-ArCu(III)-Cu(I) Catalytic Cycle: Cu(II)-Catalyzed Oxidative Arene C-H Bond Azidation with Air as an Oxidant under Ambient Conditions.
J. Org. Chem.
PUBLISHED: 11-05-2014
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On the basis of our recent discovery of high valent organocopper compounds, we have designed and achieved efficient copper(II)-catalyzed oxidative arene C-H bond azidation under very mild aerobic conditions by using NaN3 as an azide source. In the presence of a Cu(II) catalyst, a number of azacalix[1]arene[3]pyridines underwent direct arene C-H bond cupration through an electrophilic aromatic metalation pathway to form an arylcopper(II) intermediate. Oxidized by a free copper(II) ion, the arylcopper(II) intermediate was transformed into an arylcopper(III) species that subsequently cross-coupled with azide to furnish the formation of aryl azide products with the release of a copper(I) ion. Under ambient catalytic reaction conditions, the copper(I) species generated was oxidized by air into copper(II), which entered into the next catalytic cycle. Application of the method was demonstrated by the synthesis of functional azacalix[1]arene[3]pyridines by means of simple and practical functional group transformations of azide. The showcase of the Cu(II)-ArCu(II)-ArCu(III)-Cu(I) catalytic cycle would provide a new strategy for the design of copper(II)-catalyzed aerobic oxidative arene C-H bond activation and transformations.
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Identification of Hydrogen Peroxide-Secreting Cells by Cytocompatible Coating with a Hydrogel Membrane.
Anal. Chem.
PUBLISHED: 11-01-2014
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A method for identifying each cell secreting reactive oxygen species (ROS) is highly desirable to advance the understanding of the physiological and pathological processes attributed to extracellular ROS. Here, we first report a method for realizing this. The individual cells secreting hydrogen peroxide (H2O2), a common ROS, could be coated by a hydrogel membrane through a horseradish peroxidase-catalyzed reaction consuming H2O2 secreted from the cells themselves. This hydrogel membrane coating was proved to be cytocompatible. In addition, the hydrogel membrane made from an alginate derivative could be removed on demand without causing damage to the enclosed cells. These results demonstrated the feasibility of the proposed method to be an effective tool in cellular ROS studies.
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Combined CDKN1A/TP53 mutation in bladder cancer is a therapeutic target.
Mol. Cancer Ther.
PUBLISHED: 10-29-2014
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Invasive bladder cancer has high morbidity and nearly uniform mortality when metastatic, with no therapeutic improvement in many years. Although chemotherapy combined with Chk1 inhibition has been investigated in several cancer types in which TP53 mutation is seen, this combination treatment approach has not been studied in bladder cancer. Recently cancer genome sequencing efforts have identified CDKN1A (p21) mutations at 14% frequency in invasive bladder cancer, co-occurring half the time with TP53 mutations. We hypothesized that combined CDKN1A - TP53 loss would make bladder cancer sensitive to combined treatment with gemcitabine and Chk1 inhibitor. Here, we show that TP53/CDKN1A double mutant bladder cancer cell lines, 647V and RT-112, have a remarkable increase in p-Chk1 levels and G2/M arrest in response to gemcitabine treatment, with a heightened sensitivity to combination treatment with gemcitabine and either Chk1 inhibitor PF477736 or AZD7762, in comparison to other bladder cancer cell lines (either TP53 or p21 deficient). In addition, CDKN1A restoration in p21-deficient bladder cancer cells significantly reduced their sensitivity to combined treatment by protecting them from DNA damage and apoptosis. Furthermore, xenograft studies using RT-112 showed a significant synergistic effect of combined gemcitabine - PF477736 treatment on tumor growth. Our findings suggest that TP53/CDKN1A double mutant bladder cancer cells have a unique dependence on Chk1 activity for the G2/M cell cycle checkpoint in response to chemotherapy-induced DNA damage. This combination or others involving genotoxic agents-Chk kinase inhibitors is a promising therapeutic approach for bladder cancer with these mutations.
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A de novo transcriptomic analysis to reveal functional genes in Apolygus lucorum.
Insect Sci.
PUBLISHED: 10-27-2014
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The widespread planting of genetically engineered cotton producing the Cry1Ac toxin has led to significantly reduced pesticide applications since 1997. However, consequently, the number of green mirid bug (GMB), Apolygus lucorum (Meyer-Dür) has increased. So far the GMB, instead of the cotton bollworm Helicoverpa armigera (Hübner), has become the major pest in transgenic Bt cotton field and influenced cotton yield. Disproportionately, only a few studies on GMB at a molecular level have been reported. Libraries from both third instar nymph and adult were sequenced using Illumina technology, producing more than 106 million short reads and assembled into 63 029 unigenes of mean length 597 nt and N50 813 nt, ranging from 300 nt to 9771 nt. BLASTx analysis against Nr, Swissprot, GO and COG was performed to annotate these unigenes. As a result, 26 478 unigenes (42.01%) matched to known proteins and 107 immune-related, 320 digestive-related and 53 metamorphosis-related genes were detected in these annotated unigenes. Additionally, we profiled gene expression using mapping based differentially expressed genes (DEGs) strategy between the two developmental stages: nymph and adult. The results demonstrated that thousands of genes were significantly differentially expressed at different developmental stages. The transcriptome and gene expression data provided comprehensive and global gene resources of GMB. This transcriptome would improve our understanding of the molecular mechanisms of various underlying biological characteristics, including development, digestion and immunity in GMB. Therefore, these findings could help elucidate the intrinsic factors of the GMB resurgence, offering novel pest management targets for future transgenic cotton breeding. This article is protected by copyright. All rights reserved.
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Identification and Functional Characterization of Sex Pheromone Receptors in the Common Cutworm (Spodoptera litura).
Chem. Senses
PUBLISHED: 10-27-2014
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Male moths can finely discriminate the sex pheromone emitted by conspecific females from similar compounds. Pheromone receptors, expressed on the dendritic membrane of sensory neurons housed in the long trichoid sensilla of antennae, are thought to be associated with the pheromone reception. In this study, we identified and functionally characterized 4 pheromone receptors from the antennae of Spodoptera litura (Lepidoptera: Noctuidae). A tissue distribution analysis showed that the expression of the 4 SlituPRs was restricted to antennae. In addition, SlituOR6 and SlituOR13 were specifically expressed in male antennae whereas SlituOR11 and SlituOR16 were male-biased. Functional investigation by heterologous expression in Xenopus oocytes revealed that SlituOR6 was specifically tuned to the second major pheromone component, Z9,E12-14:OAc, SlituOR13 was equally tuned to Z9,E12-14:OAc and Z9-14:OAc, with a small response to the major pheromone component Z9,E11-14:OAc, SlituOR16 significantly responded to the behavioral antagonist Z9-14:OH, whereas SlituOR11 did not show response to any of the pheromone compounds tested in this study. Our results provide molecular data to better understand the mechanisms of sex pheromone detection in the moth S. litura and bring clues to investigate the evolution of the sexual communication channel in closely related species through comparison with previously reported pheromone receptors in other Spodoptera species.
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Core-Shell Nanoparticles Based on Pullulan and Poly(?-amino) Ester for Hepatoma-Targeted Codelivery of Gene and Chemotherapy Agent.
ACS Appl Mater Interfaces
PUBLISHED: 10-27-2014
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This study designs a novel nanoparticle system with core-shell structure based on pullulan and poly(?-amino) ester (PBAE) for the hepatoma-targeted codelivery of gene and chemotherapy agent. Plasmid DNA expressing green fluorescent protein (pEGFP), as a model gene, was fully condensed with cationic PBAE to form the inner core of PBAE/pEGFP polycomplex. Methotrexate (MTX), as a model chemotherapy agent, was conjugated to pullulan by ester bond to synthesize polymeric prodrug of MTX-PL. MTX-PL was then adsorbed on the surface of PBAE/pEGFP polycomplex to form MTX-PL/PBAE/pEGFP nanoparticles with a classic core-shell structure. MTX-PL was also used as a hepatoma targeting moiety, because of its specific binding affinity for asialoglycoprotein receptor (ASGPR) overexpressed by human hepatoma HepG2 cells. MTX-PL/PBAE/pEGFP nanoparticles realized the efficient transfection of pEGFP in HepG2 cells and exhibited significant inhibitory effect on the cell proliferation. In HepG2 tumor-bearing nude mice, MTX-PL/PBAE/pEGFP nanoparticles were mainly distributed in the tumor after 24 h postintravenous injection. Altogether, this novel codelivery system with a strong hepatoma-targeting property achieved simultaneous delivery of gene and chemotherapy agent into tumor at both cellular and animal levels.
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Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study.
Tumori
PUBLISHED: 10-25-2014
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Aims and background. Circulating hepatocellular carcinoma cells may be detected by reverse transcription-polymerase chain reaction. We investigated the relationship between circulating hepatocellular carcinoma cells and hepatoma patient survival after different managements and survival periods. Methods and study design. Peripheral vein blood (5 ml) samples were obtained from 113 patients with hepatocellular carcinoma and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 healthy individuals) between January 1, 2009, and December 31, 2013. To detect circulating hepatocellular carcinoma cells in peripheral blood, alpha-fetoprotein messenger RNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction. Results. Alpha-fetoprotein messenger RNA was detected in 59 blood samples from the hepatocellular carcinoma patients (59/113, 52.2%). In contrast, there were no clinical control subjects whose samples showed detectable alpha-fetoprotein messenger RNA. The presence of alpha-fetoprotein messenger RNA in blood seemed to be correlated with the stage (by TNM classification) of hepatocellular carcinoma, serum alpha-fetoprotein value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, alpha-fetoprotein messenger RNA was detected in the blood of 25 patients showing distant metastasis at extrahepatic organs (100%), in contrast to 32 of 88 cases without metastasis (36.4%). All the patients with hepatocellular carcinoma were followed. Seventeen patients with resection of a T 2 stage hepatocellular carcinoma had a survival of 3.2 years after surgical management, 38 cases with resection of a T3 stage hepatocellular carcinoma had a 1.3-year survival, and only 37 cases with T4 stage disease after different treatments except surgery survived for 0.6 years (P <0.01). Conclusions. The presence of alpha-fetoprotein messenger RNA in peripheral blood may be an indicator of circulating hepatocellular carcinoma cells, which might predict hematogenous spreading metastasis in patients with hepatocellular carcinoma and may be a poor prognostic factor for hepatocellular carcinoma patients.
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Contrast-enhanced sonography for quantitative assessment of portal hypertension in patients with liver cirrhosis.
J Ultrasound Med
PUBLISHED: 10-23-2014
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The clinical utility of contrast-enhanced sonography in portal hypertension remains unclear. We explored the feasibility of using contrast-enhanced sonography for noninvasive assessment of portal venous pressure.
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Porous cobalt, nitrogen-codoped carbon nanostructures from carbon quantum dots and VB12 and their catalytic properties for oxygen reduction.
Phys Chem Chem Phys
PUBLISHED: 10-22-2014
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The porous cobalt, nitrogen-codoped carbon materials (Co/N/C) were synthesized by a facile one-step pyrolysis of vitamin B12 (VB12) and carbon quantum dots (CQDs). Varying the initial mass ratio of CQDs and VB12 leads to controllable concentrations of Co (0% to 3.68%) and N (0% to 5.88%) after pyrolysis. The obtained Co/N/C was evaluated by oxygen reduction reaction (ORR) in both alkaline and acid media. Particularly, the Co/N/C with 1.12% Co and 2.92% N prepared at 700 °C (Co1.12/N2.92/C-700) exhibited the best catalytic ability for ORR with a cathodic peak at -0.165 and 0.185 V (vs. SCE) in 0.1 M KOH and 0.1 M HClO4 solution, respectively, which are comparable to that of Pt/C (20%). The Co1.12/N2.92/C-700 also showed long-term stability and high methanol tolerance, which outperformed commercial Pt/C (20%).
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Characterization of the mitogenome of Uropsilus gracilis and species delimitation.
Mitochondrial DNA
PUBLISHED: 10-21-2014
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Abstract The species diversity within the genus Uropsilus were underestimated: 10 species among the genus Uropsilus have been proposed. In this study, the complete mitochondrial genome of U. gracilis, with the topotype, was determined. It is 16,536?bp in length, comprising of 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes and 1 control region. The composition and arrangement of its genes are similar to most other mammals. The total base composition of the mitogenome is A, 33.4%; T, 30.3%; C, 22.7% and G, 13.6%, with a rich content of A+T pattern. We performed the similarity comparison based on 13 PCGs of three species of Asiatic shrew-like mole, U. gracilis, U. sp. 1 and U. soricipes. Pairwise sequence alignment showed that similarity data of U. gracilis versus U. sorcipes are significantly higher than those of U. gracilis versus U. sp.1. This pointed toward a cryptic species (U. sp.1) from Jiajin Mountains rather than U. gracilis.
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Surgical Correction of Anomalous Origin of One Pulmonary Artery Without Grafts in Infants.
J Card Surg
PUBLISHED: 10-21-2014
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To review the experiences in repairing the anomalous origin of one pulmonary artery in infants.
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Polarization-dependent elliptical crater morphologies formed on a silicon surface by single-shot femtosecond laser ablation.
Appl Opt
PUBLISHED: 10-17-2014
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Formation of the elliptical-shaped craters on a silicon surface is investigated comprehensively using a single shot of a femtosecond laser. It is observed that the ablation craters are elongated along the major axis of the polarization direction, while their orientation is parallel to the polarization direction. The ablation area grows and the morphology of the craters evolves from an ellipse to nearly a circle with increasing fluence. The underlying physical mechanism is revealed through numerical simulations that are based on the finite-difference time-domain technique. It is suggested that the initially formed craters or surface defects lead to the redistribution of the electric field on the silicon surface, which plays a crucial role in the creation of the elliptical-shaped craters. In addition, the field intensity becomes enhanced along the incident laser polarization direction, which determines the elliptical crater orientations.
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Four-wavelength laser based on intracavity BaWO4 Raman conversions of a dual-wavelength Q-switched Nd:YLF laser.
Opt Express
PUBLISHED: 10-17-2014
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By using diode-end-pumped acousto-optically Q-switched intracavity Raman laser configurations, we demonstrate a four-wavelength laser emitting at 1047.0, 1053.0, 1159.4 and 1166.8 nm. Two Nd:YLiF4 crystals are employed to generate 1047.0-nm and 1053.0-nm laser radiations. These two lasers are then frequency converted by a BaWO4 Raman crystal to generate 1159.4-nm and 1166.8-nm first-Stokes waves. With pulse synchronization realized, we obtain the maximum output powers of 427, 418, 423 and 332 mW for 1047.0-nm, 1053.0-nm, 1159.4-nm and 1166.8-nm lasers, respectively. The total optical-to-optical conversion efficiency is 15.1%.
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DFG-out Mode of Inhibition by an Irreversible Type-1 Inhibitor Capable of Overcoming Gate-Keeper Mutations in FGF Receptors.
ACS Chem. Biol.
PUBLISHED: 10-16-2014
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Drug-resistance acquisition through kinase gate-keeper mutations is a major hurdle in the clinic. Here, we determined the first crystal structures of the human FGFR4 kinase domain (FGFR4K) alone and complexed with ponatinib, a promiscuous type-2 (DFG-out) kinase inhibitor, and an oncogenic FGFR4K harboring the V550L gate-keeper mutation bound to FIIN-2, a new type-1 irreversible inhibitor. Remarkably, like ponatinib, FIIN-2 also binds in the DFG-out mode despite lacking a functional group necessary to occupy the pocket vacated upon the DFG-out flip. Structural analysis reveals that the covalent bond between FIIN-2 and a cysteine, uniquely present in the glycine-rich loop of FGFR kinases, facilitates the DFG-out conformation, which together with the internal flexibility of FIIN-2 enables FIIN-2 to avoid the steric clash with the gate-keeper mutation that causes the ponatinib resistance. The structural data provide a blueprint for the development of next generation anticancer inhibitors through combining the salient inhibitory mechanisms of ponatinib and FIIN-2.
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Gold-nanocrystal-enhanced bioluminescent nanocapsules.
ACS Nano
PUBLISHED: 10-13-2014
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Metal-enhanced bioluminescence presents a great opportunity to achieve ultrasensitive analysis and imaging with low bioluminescent background and enhanced luminescence. We hereby report metal-enhanced bioluminescence based on bioluminescent protein nanocapsules conjugated with gold nanocrystals. Such gold-nanocapsule complexes exhibit near 10-fold enhancement in bioluminescent intensity and are effectively delivered into the cells with outstanding stability. This work offers a class of bioluminescent nanoparticles for imaging and other applications.
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Fabrication and characterization of chitosan-collagen crosslinked membranes for corneal tissue engineering.
J Biomater Sci Polym Ed
PUBLISHED: 10-09-2014
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This article describes a chitosan-collagen composite membrane as corneal tissue-engineering biomaterials. The membrane was prepared by dissolving the chitosan into collagen with the weight ratio of 0, 15, 30, 45, 60, and 100%, followed by crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. Mechanical properties, contact angles, and optical transmittance were determined and compared between chitosan membrane and crosslinking composite membrane. As a result, the optical transparency and mechanical strength of the chitosan-collagen membranes were significantly better than that of the sample of chitosan. In addition, in vitro cell culture studies revealed that the collagen has no negative effect on the cell morphology, viability, and proliferation and possess good biocompatibility. Overall, the dendrimer crosslinked chitosan-collagen composite membranes showed promising properties that suggest that these might be suitable biomaterials for corneal tissue-engineering applications.
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Evaluating a hepatitis c quality gap: missed opportunities for HCV-related cares.
Am J Manag Care
PUBLISHED: 10-09-2014
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Objectives Diagnosis of chronic hepatitis C virus (HCV) is a 2-step process involving hepatitis C antibody (HCVab) testing followed by viral ribonucleic acid (RNA) testing. The HCV status of those with a positive HCVab without viral testing cannot be determined. This study sought to describe the HCV-related care provided to patients in this care gap. Study Design Retrospective cohort study of active patients with a positive HCVab test who did not complete viral testing. Methods Electronic medical records (EMRs) were reviewed to determine if each subject's first positive HCVab result was acknowledged by a provider. For results acknowledged, we described provider actions in response to the result. When providers performed specific clinical actions within 1 year of the positive HCVab test, we captured the type of action taken. When the unsubstantiated diagnosis was documented in the EMR, we determined if the diagnosis was mentioned by subsequent providers. Results Positive HCVab results were not acknowledged in 31% of subjects. In 35%, providers added chronic HCV to the problem list in the EMR, resulting in a higher likelihood of subsequent providers mentioning the diagnosis in their EMR documentation. In 143 subjects whose providers recommended HCV-related clinical actions within 1 year of the positive result, 45% were educated about HCV and 42% had their liver enzymes monitored. Conclusions With more widespread testing anticipated and more effective treatments available, health systems should ensure the HCV diagnostic process results in the delivery of an accurate and timely HCV diagnosis, to reduce the risk of harm to patients.
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Visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction and low-grade inflammation in a subset of irritable bowel syndrome patients.
J Zhejiang Univ Sci B
PUBLISHED: 10-09-2014
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The pathophysiology of irritable bowel syndrome (IBS) is complex and not fully understood, so the aim of this study was to evaluate whether visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction, and low-grade inflammation of the gut wall are associated with diarrhea-predominant IBS (D-IBS). Sixty-two patients with D-IBS and 20 control subjects participated in the study. Using the ascending method of limits (AML) protocol, we demonstrated that D-IBS patients had significantly lower sensory thresholds compared with healthy controls (P<0.001). Using diverse methods, especially the ischemic sensitivity test, for the first time in China, we confirmed that D-IBS patients have somatic hypersensitivity. They had a significantly higher systolic blood pressure and heart rate after a cold stimulus, indicative of autonomic cardiovascular dysfunction. Compared with the control group, D-IBS patients had a significantly higher level of calprotectin (P<0.001). We also found significant correlations between visceral and somatic hypersensitivity, visceral hypersensitivity and autonomic cardiovascular dysfunction, and somatic hypersensitivity and autonomic cardiovascular dysfunction. Our findings may provide valuable suggestions for the treatment of D-IBS.
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Comparing score tests and other local dependence diagnostics for the graded response model.
Br J Math Stat Psychol
PUBLISHED: 10-07-2014
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Score tests for identifying locally dependent item pairs have been proposed for binary item response models. In this article, both the bifactor and the threshold shift score tests are generalized to the graded response model. For the bifactor test, the generalization is straightforward; it adds one secondary dimension associated only with one pair of items. For the threshold shift test, however, multiple generalizations are possible: in particular, conditional, uniform, and linear shift tests are discussed in this article. Simulation studies show that all of the score tests have accurate Type I error rates given large enough samples, although their small-sample behaviour is not as good as that of Pearson's ?2 and M2 as proposed in other studies for the purpose of local dependence (LD) detection. All score tests have the highest power to detect the LD which is consistent with their parametric form, and in this case they are uniformly more powerful than ?2 and M2 ; even wrongly specified score tests are more powerful than ?2 and M2 in most conditions. An example using empirical data is provided for illustration.
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The impact of cellulose nanocrystals on the aggregation and initial adhesion of Pseudomonas fluorescens bacteria.
Soft Matter
PUBLISHED: 10-07-2014
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Deposition on silica surfaces of two Pseudomonas fluorescens strains (CHA0 and CHA19-WS) having different extracellular polymeric substance (EPS) producing capacities was studied in the absence and presence of cellulose nanocrystals (CNCs). Batch (batch soaking) and continuous flow (quartz crystal microbalance with dissipation) methods were used to evaluate the impact of CNCs on bacterial initial adhesion. This study demonstrated that bacterial initial adhesion to solid surfaces can be significantly hindered by CNCs using both methods. In the presence of CNCs, it was observed that bacteria with more EPS aggregated more significantly compared to bacteria with less EPS, and that bacterial deposition under this condition decreased to a greater extent. The classic DLVO theory failed to predict bacterial adhesion behavior in this study. A detailed discussion is provided regarding potential antibacterial adhesion mechanisms of CNCs.
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[Combination analysis of new drug discovery with "Xiaohe Silian" method and traditional Chinese medicine clinical pharmacy].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-04-2014
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With the kernel of efficacy, "Xiaohe Silian" was a pattern and method for new drug discovery which was constituted with "metabolism-efficacy, toxicity-efficacy, quality-efficacy and structure-efficacy". Its connotation was in keeping with traditional Chinese medicine (TCM) clinical pharmacy. This paper systematically summarized the research method of new drug discovery practice process for TCM. To avoid western drug like in TCM new drug discovery, we carried out combination analysis with TCM clinical pharmacy. The correlation analysis between basic elements of "Xiaohe Silian(n) and TCM clinical pharmacy was studied to guarantee this method could integrate closely with TCM clinic from all angles. Hence, this method aimed to provide a new method for TCM new drug discovery on the basis of TCM clinical pharmacy with insisting on holistic view of multicomponent study, kinetic view of metabolic process when the curative effect occurred and molecular material view of quality control and structure-activity exposition.
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The Relationship Between Disability-Adjusted Life Years of Cataracts and Ambient Erythemal Ultraviolet Radiation in China.
J Epidemiol
PUBLISHED: 09-30-2014
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Background: Cataracts are one of the major public health problems worldwide. Ultraviolet radiation (UVR) is one of the risk factors for cataract development. We analyzed the relationship between disability-adjusted life year (DALY) rates of cataracts and UVR exposure in China.Methods: DALY rates of cataracts and UVR exposure in 31 regions of China were calculated based on data from the Second China National Sample Survey on Disability and the United States' National Aeronautics and Space Administration database. The relationship between the DALY rates of cataracts and UVR was estimated by Spearman rank correlation analysis and linear regression analysis.Results: The elderly (?65 years) had higher DALY rates of cataracts than the whole population. The DALY rate of cataracts in the agricultural population was higher than that observed in the non-agricultural population. The DALY rates of cataracts were positively associated with UVR The DALY rates of cataracts in regions with higher UVR were higher than those in regions with lower UVR. An increase in the daily ambient erythemal UVR of 1000 J/m(2) was associated with an increase in the DALY rates of cataracts by 92 DALYs/100 000 (R(2) = 0.676) among the whole population, 34 DALYs/100 000 among the population <65 years old (R(2) = 0.423), 607 DALYs/100 000 among the population aged 65-74 years (R(2) = 0.617), and by 1342 DALYs/100 000 among the population ?75 years old (R(2) = 0.758).Conclusions: DALY rates of cataracts increased with increases in UVR exposure in 31 regions of China. Greater exposure to UVR increases the disease burden of cataracts in the whole population, especially in the elderly and among the agricultural population.
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[Effect of urapidil combined with phentolamine on hypertension during extracorporeal circulation].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-30-2014
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To study the effect of urapidil combined with phentolamine in the management of hypertension during extracorporeal circulation.
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Nanoparticle tension probes patterned at the nanoscale: impact of integrin clustering on force transmission.
Nano Lett.
PUBLISHED: 09-30-2014
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Herein we aimed to understand how nanoscale clustering of RGD ligands alters the mechano-regulation of their integrin receptors. We combined molecular tension fluorescence microscopy with block copolymer micelle nanolithography to fabricate substrates with arrays of precisely spaced probes that can generate a 10-fold fluorescence response to pN-forces. We found that the mechanism of sensing ligand spacing is force-mediated. This strategy is broadly applicable to investigating receptor clustering and its role in mechanotransduction pathways.
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Metallofullerenes Encaging Mixed-Metal Clusters: Synthesis and Structural Studies of Gdx Ho3-x N@C80 and Gdx Lu3-x N@C80.
Chemphyschem
PUBLISHED: 09-28-2014
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Metallofullerenes of Gdx Ho3-x N@C80 and Gdx Lu3-x N@C80 encapsulating mixed-metal nitride clusters were synthesized. Spectroscopic characterization of Gdx Ho3-x N@C80 and Gdx Lu3-x N@C80 was employed to reveal their structural and vibrational properties. The structural properties of these species were analyzed by using theoretical calculations. The studies of Gdx Ho3-x N@C80 and Gdx Lu3-x N@C80 laid the foundations for these species to be used as multifunctional molecules.
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Reinstatement of Distantasca Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae: Empoascini) as a valid genus with new species and new combinations.
Zootaxa
PUBLISHED: 09-26-2014
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Distantasca Dworakowska originally established as a genus but more recently has been treated as a subgenus of Empoasca Walsh. Here we reinstate Distantasca as a valid genus and provide a revised diagnosis. New combinations created are Distantasca atika (Dworakowska), n. comb., Distantasca barawa (Dworakowska), n. comb., Distantasca bulbosa (Dworakowska), n. comb., Distantasca latava (Dworakowska), n. comb., Distantasca latibasis (Zhang & Liu), n. comb., Distantasca paraterminalis (Qin & Zhang), n. comb., Distantasca riora (Dworakowska), n. comb., Distantasca rokasa (Dworakowska), n. comb., Distantasca serratipenis (Qin & Zhang), n. comb., Distantasca tiaca (Dworakowska), n. comb., Distantasca tna (Dworakowska), n. comb., Distantasca tuberculata (Zhang & Liu), n. comb., all from Empoasca (Distantasca). Distantasca terminalis (Distant) and D. faciata Dworakowska are reinstated from Empoasca (Distantasca). Two new species, Distantasca longihamatilis Zhang & Liu and Distantasca ricina Zhang & Liu spp. nov. are described and illustrated. Empoasca (Empoasca) smithi Fletcher & Donaldson, 1992 is transferred into the genus as Distantasca smithi (Fletcher & Donaldson).
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IKK? deficiency in myeloid cells ameliorates Alzheimer's disease-related symptoms and pathology.
J. Neurosci.
PUBLISHED: 09-26-2014
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Alzheimer's disease (AD) is characterized by extracellular amyloid-? (A?) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and A? clearance. However, studies examining innate immunity in A? pathology and neuronal degeneration have produced conflicting results. In this study, we investigated the pathogenic role of innate immunity in AD by ablating a key signaling molecule, IKK?, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKK? in myeloid cells, especially microglia, simultaneously reduced inflammatory activation and A? load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKK? deficiency enhanced microglial recruitment to A? deposits and facilitated A? internalization, perhaps by inhibiting TGF-?-SMAD2/3 signaling, but did not affect A? production and efflux. Therefore, inhibition of IKK? signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing A? clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression.
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Efficient Conversion of Spermatogonial Stem Cells to Phenotypic and Functional Dopaminergic Neurons via the PI3K/Akt and P21/Smurf2/Nolz1 Pathway.
Mol. Neurobiol.
PUBLISHED: 09-24-2014
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Parkinson's disease (PD) is a common neurodegenerative syndrome characterized by loss of midbrain dopaminergic (DA) neurons. Generation of functional dopaminergic (DA) neurons is of unusual significance for treating Parkinson's disease (PD). However, direct conversion of spermatogonial stem cells (SSCs) to functional DA neurons without being reprogrammed to a pluripotent status has not been achieved. Here, we report an efficient approach to obtain morphological, phenotypic, and functional DA neurons from SSCs using a specific combination of olfactory ensheathing cell-conditioned medium (OECCM) and several defined growth factors (DGF). By following the current protocol, direct conversion of SSCs (both SSC line and primary SSCs) to neural cells and DA neurons was demonstrated by expression of numerous phenotypic genes and proteins for neural cells, as well as cell morphological features. More significantly, SSCs-derived DA neurons acquired neuronal functional properties such as synapse formation, electrophysiology activity, and dopamine secretion. Furthermore, PI3K/Akt pathway and p21/Nolz1 cascades were activated whereas Smurf2 was inactivated, leading to cell cycle exit during the conversion of SSCs into DA neurons. Collectively, this study could provide sufficient neural cells from SSCs for applications in the treatment of PD and offers novel insights into mechanisms underlying neural system development from the line of germ cells.
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Dental caries status and oral health behavior among civilian pilots.
Aviat Space Environ Med
PUBLISHED: 09-24-2014
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This study was aimed at investigating the caries status of Chinese civilian pilots and the relationship between caries and oral health behaviors, including sugar intake, smoking, alcohol consumption, tooth brushing, and dental check-up attendance.
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Aflatoxin B? degradation by a Pseudomonas strain.
Toxins (Basel)
PUBLISHED: 09-23-2014
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Aflatoxin B1 (AFB1), one of the most potent naturally occurring mutagens and carcinogens, causes significant threats to the food industry and animal production. In this study, 25 bacteria isolates were collected from grain kernels and soils displaying AFB1 reduction activity. Based on its degradation effectiveness, isolate N17-1 was selected for further characterization and identified as Pseudomonas aeruginosa. P. aeruginosa N17-1 could degrade AFB?, AFB? and AFM? by 82.8%, 46.8% and 31.9% after incubation in Nutrient Broth (NB) medium at 37 °C for 72 h, respectively. The culture supernatant of isolate N17-1 degraded AFB? effectively, whereas the viable cells and intra cell extracts were far less effective. Factors influencing AFB1 degradation by the culture supernatant were investigated. Maximum degradation was observed at 55 °C. Ions Mn²? and Cu²? were activators for AFB1 degradation, however, ions Mg²?, Li?, Zn²?, Se²?, Fe³? were strong inhibitors. Treatments with proteinase K and proteinase K plus SDS significantly reduced the degradation activity of the culture supernatant. No degradation products were observed based on preliminary LC-QTOF/MS analysis, indicating AFB? was metabolized to degradation products with chemical properties different from that of AFB?. The results indicated that the degradation of AFB? by P. aeruginosa N17-1 was enzymatic and could have a great potential in industrial applications. This is the first report indicating that the isolate of P. aeruginosa possesses the ability to degrade aflatoxin.
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Long noncoding RNA expression in dermal papilla cells contributes to hairy gene regulation.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-22-2014
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Dermal papilla (DP) cells may be the source of dermal-derived signaling molecules involved in hair-follicle development and postnatal hair cycling. Early-passage DP cells can induce hair growth in vivo, but, on further culture, this ability is lost. The cellular mechanisms underlying the hair-follicle induction property of early-passage DP cells are unclear. Long noncoding RNAs (lncRNAs) are an important class of genes involved in various biological functions. They are aberrantly expressed and play roles in the regulation of the Wnt signaling pathway, a critical point in maintaining hair-induction activity. LncRNA microarray revealed 1683 upregulated and 1773 downregulated lncRNAs in passage-4 DP cells compare with passage-10 DP cells. To investigate the relation between lncRNAs and coding genes in WNT signaling, we constructed a coding-noncoding gene co-expression network using lncRNAs and coding genes that were differentially expressed between the passage-4 and -10 DP cells. RP11-766N7.3, H19 and HOTAIR are specific lncRNAs that were aberrantly expressed in DP cells and played an important role in regulating Wnt signaling. This study may provide potential targets for discovering the hair-follicle induction mechanism of early-passage DP cells.
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DNA-PKcs deficiency inhibits glioblastoma cell-derived angiogenesis after ionizing radiation.
J. Cell. Physiol.
PUBLISHED: 09-21-2014
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DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a critical role in non-homologous end-joining repair of DNA double-strand breaks (DSB) induced by ionizing radiation (IR). Little is known, however, regarding the relationship between DNA-PKcs and IR-induced angiogenesis; thus, in this study we aimed to further elucidate this relationship. Our findings revealed that lack of DNA-PKcs expression or activity sensitized glioma cells to radiation due to the defective DNA DSB repairs and inhibition of phosphorylated Akt(Ser473) . Moreover, DNA-PKcs deficiency apparently mitigated IR-induced migration, invasion and tube formation of human microvascular endothelial cell (HMEC-1) in conditioned media derived from irradiated DNA-PKcs mutant M059J glioma cells or M059K glioma cells that have inhibited DNA-PKcs kinase activity due to the specific inhibitor NU7026 or siRNA knockdown. Moreover, IR-elevated vascular endothelial growth factor (VEGF) secretion was abrogated by DNA-PKcs suppression. Supplemental VEGF antibody to irradiated-conditioned media was negated enhanced cell motility with a concomitant decrease in phosphorylation of the FAK (Try925) and Src(Try416) . Furthermore, DNA-PKcs suppression was markedly abrogated in IR-induced transcription factor hypoxia inducible factor-1? (HIF-1?) accumulation, which is related to activation of VEGF transcription. These findings, taken together, demonstrate that depletion of DNA-PKcs in glioblastoma cells at least partly suppressed IR-inflicted migration, invasion and tube formation of HMEC-1 cells, which may be associated with the reduced HIF-1? level and VEGF secretion. Inhibition of DNA-PKcs may be a promising therapeutic approach to enhance radio-therapeutic efficacy for glioblastoma by hindering its angiogenesis. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.
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Hospitalization for Toxicity in Patients Treated With Rituximab.
Am. J. Clin. Oncol.
PUBLISHED: 09-20-2014
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To estimate the rates of hospitalizations in patients within 12 months after the first rituximab administration.
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[Influence of cationic cyclopeptide on microstructure and permeability of Caco-2 cell membrane].
Yao Xue Xue Bao
PUBLISHED: 09-20-2014
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The microstructure of cationic cyclopeptide (TD-34) treated Caco-2 cell membrane was observed, and we discussed the relationship between membrane structure and insulin transmembrane permeability. Atomic force microscope (AFM) was used to observe living cell membrane in air condition and tapping mode. Results showed that the surface of Caco-2 cell membrane treated with TD-34 lost its smoothness and nearly doubled its roughness. Apparent permeability coefficients (P(app)) of insulin in Caco-2 cell monolayers increased 2.5 times. In conclusion, AFM can be used to observe microstructure of cationic cyclopeptide treated cell membrane and cationic cyclopeptide enhanced insulin delivery across Caco-2 cell membrane by increasing membrane fluidity.
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Studies on the effect of thymine-mercury-thymine stem as a structural or functional motif in DNAzymes.
Nucleosides Nucleotides Nucleic Acids
PUBLISHED: 09-16-2014
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T-Hg-T base pair formation has been demonstrated to be compatible with duplex DNA context, with considerable thermal stability contribution. Here, the T-Hg-T stem in two small DNAzymes 8-17 and 10-23 was studied for its structural and functional roles. The recognition arm 5' to the cleavage site of 10-23 DNAzyme complex and the stem in the catalytic loop of 8-17 DNAzyme could be replaced by consecutive T-Hg-T stem of different length. The linear relationship between the activity of the complex 10-23DZ-6T+D19-6T and the concentration of Hg(2+) demonstrated that the T-Hg-T stem contributes thermal stability of the recognition arm binding. The effect of T-Hg-T stem in the catalytic core of 8-17 DNAzyme and the position-dependent effect in 10-23 DNAzyme demonstrated that T-Hg-T base pair is not compatible with canonical base pairs in playing the functions of nucleic acids.
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Thioclava indica sp. nov., isolated from surface seawater of the Indian Ocean.
Antonie Van Leeuwenhoek
PUBLISHED: 09-09-2014
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A short-rod shaped, non-motile and Gram-negative strain, designated as DT23-4(T), was isolated from a dotriacontane-degrading bacterial consortium, enriched in the surface seawater of the Indian Ocean. To delineate its taxonomic position, strain DT23-4(T) was subjected to polyphasic characterization. Strain DT23-4(T) can grow at temperatures from 10 to 41 °C, in the range of pH 6-10 and at salinities from 0 to 18 % (w/v). It is positive for denitrification, oxidase and catalase, but negative for gelatin hydrolysis and indole production. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain DT23-4(T) affiliates to the genus Thioclava, sharing high sequence similarity to Thioclava dalianensis DLFJ1-1(T) (98.2 %), Thioclava atlantica 13D2W-2(T) (96.8 %), Thioclava pacifica TL 2(T) (95.9 %) and less than 95.7 % with other species of the family Rhodobacteraceae. The digital DNA:DNA hybridization (dDDH) pairwise values between strain DT23-4(T) and T. dalianensis DLFJ1-1(T), T. atlantica 13D2W-2(T) and T. pacifica TL 2(T) were 21.5 ± 2.3, 20.6 ± 2.3 and 20.9 ± 2.3 %, respectively. Similarly, the average nucleotide identity values between strain DT23-4(T) and these three type strains were 78.0, 77.1 and 77.3 %, respectively. The principal fatty acid was identified as Summed Feature 8 (C18:1 ?7c/?6c) (81.9 %). The quinone of strain DT23-4(T) was identified as Q10 (100 %). The polar lipids of strain DT23-4(T) were found to contain phosphatidylethanolamine, phosphatidylglycerol, two glycolipids and four phospholipids. The genomic DNA G+C content was determined to be 60.3 mol%. On the basis of genotypic, phenotypic and chemotaxonomic analyses, strain DT23-4(T) can be concluded to represent a novel species of the genus Thioclava, for which the name Thioclava indica sp. nov. is proposed, with the type strain DT23-4(T) (= MCCC 1A00513(T) = LMG 27698(T) = KCTC 33533(T)).
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A new method to determine whether ossified posterior longitudinal ligament can be resected completely and safely: spinal canal "Rule of Nine" on axial computed tomography.
Eur Spine J
PUBLISHED: 09-06-2014
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To introduce the new method of spinal canal "Rule of Nine" on axial computed tomography (CT) to determine whether ossified posterior longitudinal ligament (OPLL) can be resected completely and safely.
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Applications of Legionella pneumophila protein FLA and PILE in serological diagnosis.
Clin. Lab.
PUBLISHED: 09-05-2014
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Serological testing for antibody against Legionella pneumophila (LP) is often the primary method of screening for possible Lp infections.
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[Screening and analysis of plasma microRNA profile in benzene exposed workers].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 09-04-2014
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To find out and analyze differentially expressed miRNAs in the plasma of benzene exposed workers, and explore the potential roles of plasma miRNAs in the development of hematologic toxicity induced by benzene exposure.
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Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1.
Elife
PUBLISHED: 09-03-2014
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Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced disruption of TLR4:Siglec E/F interactions. Absence of Neu1 in hematopoietic cells or systematic treatment with sialidase inhibitor Neu5Gc2en protected mice against endotoxemia. Our data raised an intriguing possibility of a broad repression of TLR function by Siglecs and a sialidase-mediated de-repression that allows positive feedback of TLR activation during infection.
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RISK FACTORS FOR MORTALITY IN CHINESE PATIENTS ON CONTINUOUS AMBULATORY PERITONEAL DIALYSIS.
Perit Dial Int
PUBLISHED: 09-02-2014
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? Objective: The intent of this study was to evaluate the clinical outcome and risk factors affecting mortality of the continuous ambulatory peritoneal dialysis (CAPD) patients in a single peritoneal dialysis (PD) center over a period of 10years. ? Patients and methods: We retrospectively analyzed patients on PD from June 2001 to June 2011. The clinical and biochemical data were collected from the medical records. Clinical variables included gender, age at the start of PD, smoking status, body mass index (BMI), cause of end-stage renal disease (ESRD), presence of diabetes mellitus and blood pressure. Biochemical variables included hemoglobin, urine volume, residual renal function (RRF), serum albumin, blood urea nitrogen (BUN), creatinine, total cholesterol, triglyceride, comorbidities, and outcomes. Survival curves were made by the Kaplan-Meier method. Univariate and multivariate analyses to identify mortality risk factors were performed using the Cox proportional hazard regression model. ? Results: A total of 421 patients were enrolled, 269 of whom were male (63.9%). The mean age at the start of PD was 57.9 ± 14.8 years. Chronic glomerulonephritis was the most common cause of ESRD (39.4%). Estimation of patient survival by Kaplan-Meier was 92.5%, 80.2%, 74.4%, and 55.7% at 1, 3, 5, and 10 years, respectively. Patient survival was associated with age (hazard ratio [HR]: 1.641 [1.027 - 2.622], p = 0.038), cardiovascular disease (HR: 1.731 [1.08 - 2.774], p = 0.023), hypertriglyceridemia (HR: 1.782 [1.11 - 2.858], p = 0.017) in the Cox proportional hazards model analysis. Estimation of technique survival by Kaplan-Meier was 86.7%, 68.8%, 55.7%, and 37.4% at 1, 3, 5, and 10 years, respectively. In the Cox proportional hazards model analysis, age (HR: 1.672 [1.176-2.377], p=0.004) and hypertriglyceridemia (HR: 1.511 [1.050-2.174], p = 0.026) predicted technique failure. ? Conclusion: The PD patients in our center exhibited comparable or even superior patient survival and technical survival rates, compared with reports from other centers in China and other countries.
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Tetramethoxychalcone, a chalcone derivative, suppresses proliferation, blocks cell cycle progression, and induces apoptosis of human ovarian cancer cells.
PLoS ONE
PUBLISHED: 09-02-2014
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In the present study, we investigated the in vitro antitumor functions of a synthetic chalcone derivative 4,3',4',5'- tetramethoxychalcone (TMOC) in ovarian cancer cells. We found that TMOC inhibited the proliferation and colony formation of cisplatin sensitive cell line A2780 and resistant cell line A2780/CDDP, as well as ovarian cancer cell line SKOV3 in a time- and dose-dependent manner. Treatment of A2780 cells with TMOC resulted in G0/G1 cell cycle arrest through the down-regulation of cyclin D1 and CDK4, and the up-regulation of p16, p21 and p27 proteins. We demonstrated that TMOC might induce cell apoptosis through suppressing Bcl-2 and Bcl-xL, but enhancing the expression of Bax and the cleavage of PARP-1. Treatment of TMOC also reduced the invasion and migration of A2780 cells. Finally, we found that TMOC inhibited the constitutive activation of STAT3 signaling pathway and induced the expression of the tumor suppressor PTEN regardless of the p53 status in cell lines. These data suggest that TMOC may be developed as a potential chemotherapeutic agent to effectively treat certain cancers including ovarian cancer.
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2-(1H-Benzimidazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol, a Benzimidazole Derivative, Inhibits T Cell Proliferation Involving H+/K+-ATPase Inhibition.
Molecules
PUBLISHED: 09-01-2014
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In this study, a benzimidazole derivative named BMT-1 is revealed as a potential immunomodulatory agent. BMT-1 inhibits the activity of H+/K+-ATPases from anti-CD3/CD28 activated T cells. Furthermore, inhibition the H+/K+-ATPases by use of BMT-1 should lead to intracellular acidification, inhibiting T cell proliferation. To explore this possibility, the effect of BMT-1 on intracellular pH changes was examined by using BCECF as a pH-dependent fluorescent dye. Interestingly, increases in the pHi were observed in activated T cells, and T cells treated with BMT-1 showed a more acidic intracellular pH. Finally, BMT-1 targeted the H+/K+-ATPases and inhibited the proliferative response of anti-CD3/CD28-stimulated T cells. A cell cycle analysis indicated that BMT-1 arrested the cell cycle progression of activated T cells from the G1 to the S phase without affecting CD25 expression or interleukin-2 (IL-2) production; treating IL-2-dependent PBMCs with BMT-1 also led to the inhibition of cell proliferation. Taken together, these findings demonstrate that BMT-1 inhibits the proliferation of T cells by interfering with H+/K+-ATPases and down-regulating intracellular pHi. This molecule may be an interesting lead compound for the development of new immunomodulatory agents.
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Effects of temperature and additives on the thermal stability of glucoamylase from Aspergillus niger.
J. Microbiol. Biotechnol.
PUBLISHED: 09-01-2014
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GAM-1 and GAM-2, two themostable glucoamylases from Aspergillus niger B-30, possess different molecular mass, glycosylation and thermal stability. In the present study, the effects of additives on the thermal inactivation of GAM-1 and GAM-2 were investigated. The half-lives of GAM-1 and GAM-2 at 70 ºC were 45 min and 216 min, respectively. Data obtained from fluorescence spectroscopy, circular dichroism (CD) spectroscopy, UV absorption spectroscopy and dynamic light scattering (DLS) demonstrated that during the thermal inactivation progress, combining with the loss of helical structure and majority of the tertiary structure, tryptophan residues were partial exposures and further lead to glucoamylases aggregating. The thermal stability of GAM-1 and GAM-2 was largely improved in the presence of sorbitol and trehalose. Results from spectroscopy and Native-PAGE confirmed that sorbitol and trehalose maintained the native state of glucoamylases and prevented its thermal aggregation. The loss of hydrophobic bonding and helical structure were responsible for the decrease of glucoamylases activity. Additionally, sorbitol and trehalose significantly increased substrate affinity and catalytic efficiency of the two glucoamylases. Our results displayed an insight into the thermal inactivation of glucoamylases and provided an important base for industrial applications of the thermal stability glucoamylases.
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Wetlands explain most in the genetic divergence pattern of Oncomelania hupensis.
Infect. Genet. Evol.
PUBLISHED: 08-23-2014
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Understanding the divergence patterns of hosts could shed lights on the prediction of their parasite transmission. No effort has been devoted to understand the drivers of genetic divergence pattern of Oncomelania hupensis, the only intermediate host of Schistosoma japonicum. Based on a compilation of two O. hupensis gene datasets covering a wide geographic range in China and an array of geographical distance and environmental dissimilarity metrics built from earth observation data and ecological niche modeling, we conducted causal modeling analysis via simple, partial Mantel test and local polynomial fitting to understand the interactions among isolation-by-distance, isolation-by-environment, and genetic divergence. We found that geography contributes more to genetic divergence than environmental isolation, and among all variables involved, wetland showed the strongest correlation with the genetic pairwise distances. These results suggested that in China, O. hupensis dispersal is strongly linked to the distribution of wetlands, and the current divergence pattern of both O. hupensis and schistosomiasis might be altered due to the changed wetland pattern with the accomplishment of the Three Gorges Dam and the South-to-North water transfer project.
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Apoptotic induction of lung adenocarcinoma A549 cells infected by recombinant RVG Newcastle disease virus (rL?RVG) in vitro.
Mol Med Rep
PUBLISHED: 08-22-2014
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Newcastle disease virus (NDV) is a member of the genus Avulavirus in the Paramyxoviridae family and its antitumor properties depend on its ability to kill malignant cells while not affecting normal cells. The present study investigated a recombinant avirulent NDV LaSota strain (wild?type NDV strain) expressing the rabies virus glycoprotein (rL?RVG), examined its oncolytic effect on the lung adenocarcinoma A549 cell line and evaluated its potential to serve as a vaccine against lung cancer. A549 cells were infected with the rL?RVG virus and analyzed by MTT, western blot, polymerase chain reaction (PCR), immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick end labeling and flow?cytometric analyses. PCR, western blot and immuno?uorescence showed that the RVG gene and protein were stably expressed in A549 cells following infection with rL?RVG. The growth of A549 cells in the rL?RVG group was inhibited more effectively compared to those infected with the wild?type NDV strain. MTT results showed that cell growth inhibition rates in the rL?RVG group were significantly higher than those in the NDV group (P<0.05). Early apoptosis in the rL?RVG group was also more evident, with the apoptotic index being increased in rL?RVG group. The expression of the pro?apoptotic proteins caspase?3, ?8 and ?9 increased. The expression of caspase?3 decreased following application of the broad?speci?city caspase inhibitor Z?VAD?FMK. However, the expression of the inhibitory apoptosis protein B?cell lymphoma 2 (bcl?2) did not change, but bcl?2?associated X/bcl?2 ratio was higher in the rL?RVG group than that in the NDV group. The rL?RVG strain was able to suppress lung cancer cell growth and promote lung cancer cell apoptosis to a greater extent than the wild?type NDV strain. Therefore, the rL?RVG strain is a potent antitumor agent.
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Antioxidant neolignan and phenolic glucosides from the fruit of Euterpe oleracea.
Fitoterapia
PUBLISHED: 08-15-2014
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Three new glucosides, namely, (-)-7R8S-7',8'-dihydroxy-dihydrodehydroconiferyl alcohol-9-O-?-d-glucopyranoside (1), (+)-7S8R-7',8'-dihydroxy-dihydrodehydroconiferyl alcohol-9-O-?-d-glucopyranoside (2) and 4-hydroxy-2-methoxyphenyl 1-O-[6-(hydrogen 3-hydroxy-3-methylpentanedioate)]-?-d-glucopyranoside (3), along with 6 known compounds were isolated from the fruit of Euterpe oleracea Mart. Their structures were elucidated based on spectroscopic analyses including NMR, HR-ESI-MS and CD. All the isolated compounds demonstrated significant antioxidant activity and 2 displayed moderate cytotoxicity against HL-60 cells.
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Hepatoprotective and antioxidant activities of extracts from Salvia¿Nelumbinis naturalis against nonalcoholic steatohepatitis induced by methionine- and choline-deficient diet in mice.
J Transl Med
PUBLISHED: 08-13-2014
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BackgroundNonalcoholic steatohepatitis (NASH), the advanced stage of nonalcoholic fatty liver disease that is characterized by both steatosis and severe injury in liver, still lacks efficient treatment. The traditional Chinese formula Salvia¿Nelumbinis naturalis (SNN) is effectively applied to improve the symptoms of nonalcoholic simple fatty liver (NAFL) patients. Previous studies have confirmed that SNN could reduce the liver lipid deposition and serum transaminases of NAFL experimental models. This study aims to determine whether SNN is effective for murine NASH model and investigate the underlying pharmacological mechanisms.MethodsC57BL/6 J mice were fed with methionine- and choline-deficient (MCD) diet for six weeks to induce NASH. Simultaneously, SNN or saline was intragastrically administered daily to the mice in the SNN or model group, respectively. A standard diet was given to the control mice. Serum biochemical indices and tumor necrosis factor-¿ were measured. Liver histopathology was observed, and the contents of triglycerides and lipid peroxide malondialdehyde (MDA) in liver homogenates were evaluated. The hepatic expression and/or activation of genes associated with inflammation, apoptosis, and oxidative stress were determined by quantitative RT-PCR or Western blot analysis.ResultsThe prominent liver steatosis displayed in the NASH model was prevented by SNN. The liver injury of NASH mice was obviously manifested by the increased levels of serum transaminases and bilirubin, as well as the lobular inflammation, elevated pro-inflammatory cytokines, and upregulated apoptosis in liver tissues. SNN administration improved the aforementioned pathological changes. The increased hepatic levels of MDA and cytochrome P450 2E1 of the model confirmed the unregulated balance of oxidative stress. The hepatic expression of nuclear factor erythroid 2-related factor 2 and its target genes decreased, whereas c-Jun N-terminal kinase activation in the model mice increased. Treating the mice with SNN significantly improved oxidative stress-related harmful factors.ConclusionsThis study shows that SNN can protect the liver from severe steatosis and damage induced by MCD diet, which suggests the potential use of SNN on the treatment of NASH patient. The results also indicate that improving the hepatic antioxidant capability of the liver may contribute to the underlying hepatoprotective mechanism.
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Hybrid ZnO Nanorod-Polymer Brush Hierarchically Nanostructured Substrate for Sensitive Antibody Microarrays.
Adv. Mater. Weinheim
PUBLISHED: 08-13-2014
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A hierarchically nanostructured organic-inorganic hybrid substrate comprising randomly oriented ZnO nanorods on glass slide with coaxially tethered dense polymer brush, POEGMA-co-GMA is reported for highly sensitive antibody microassay, achieving excellent detection specificity, and superior detection limit of as low as 100 fg mL(-1) for biomarkers in human serum within 1 h assay time.
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The comparison of minimally invasive percutaneous nephrolithotomy and retrograde intrarenal surgery for stones larger than 2 cm in patients with a solitary kidney: a matched-pair analysis.
World J Urol
PUBLISHED: 08-13-2014
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To compare the treatment outcomes between retrograde intrarenal surgery (RIRS) and minimally invasive percutaneous nephrolithotomy (MPCNL) for the management of stones larger than 2 cm in patients with solitary kidney.
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Effect of human interferon-?1 recombinant adenovirus on a gastric cancer orthotopic transplantation model.
Exp Ther Med
PUBLISHED: 08-11-2014
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The aim of the present study was to investigate the effect of human interferon-?1 recombinant adenovirus (r-Ad-hIFN-?1) on gastric carcinoma. Human SGC-7901 cells were utilized to create an orthotopic implantation model of gastric cancer in nude mice through sterile surgery. The mice were randomly divided into three groups: Phosphate-buffered saline control (blank), adenovirus encoding bacterial ?-galactosidase (Ad-Lac Z) empty vector and r-Ad-hIFN-?1. Tumor size was measured every seven days. After three weeks of treatment, the tumors in the mice were detected by abdominal B ultrasound. The cDNA of IFN-?1 expression in skeletal muscle was detected by a reverse transcription polymerase chain reaction and IFN-?1 protein expression in the tumors was detected by western blot analysis and immunohistochemistry. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays were conducted to analyze the proportion of natural killer (NK) cells in the spleen and the rate of cell apoptosis in tumor paraffin sections. Prior to sacrifice, the size of the tumors in the r-Ad-hIFN-?1, Ad-Lac Z and blank groups was 184.29±10.84 mm(3), 234.62±10.59 mm(3) and 253.18±7.69 mm(3), respectively (P<0.001). The lymph node metastasis in the abdominal cavity was 0% in the r-Ad-hIFN-?1 group, 50% in the Ad-Lac Z group and 80% in the blank group (P<0.005). Furthermore, IFN-?1 mRNA and protein were highly expressed in the r-Ad-hIFN-?1 group, and the apoptosis rate in the r-Ad-hIFN-?1 group was higher than that in the Ad-Lac Z and blank groups. The proportion of NK cells in the spleens of nude mice in the r-Ad-hIFN-?1, Ad-Lac Z and blank groups was 26.53±1.54, 17.70±1.09 and 16.35±1.43%, respectively (P<0.001). The TUNEL results showed there was significantly more severe apoptosis in the r-Ad-hIFN-?1 group than that in the two other groups. The apoptosis indices in the r-Ad-hIFN-?1, Ad-Lac Z and blank groups were 0.772±0.075, 0.329±0.169 and 0.265±0.049, respectively. In conclusion, the r-Ad-hIFN-?1 significantly inhibited human gastric cancer, possibly by promoting apoptosis of the tumors and stimulating immunological function.
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Effects of Ginsenoside Rg1 on the Expression of Toll-Like Receptor 3, 4 and Their Signalling Transduction Factors in the NG108-15 Murine Neuroglial Cell Line.
Molecules
PUBLISHED: 08-10-2014
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As one of the most important components of Panax ginseng, ginsenoside Rg1 has certain anti-aging effects, improving the activity of learning and memory. Studies have showed that ginsenoside Rg1 improves the memory impairment associated with Alzheimer's disease (AD). In this study, the effects of ginsenoside Rg1 were investigated through the activity of toll-like receptor (TLR) 3, TLR4 and their signaling transduction pathways in amyloid ? peptide 25-35 (A?25-35) induced AD cell model. Thus we investigated several critical components of the TLR pathway. The neuroglial cell line NG108-15 was stimulated with or without A?25-35, while different concentrations of ginsenoside Rg1 were administered. After 24 h, tumor necrosis factor-? (TNF-?), interferon-? (IFN-?) in cell supernatant and inducible nitric oxide synthase (iNOS) in cell lysate supernatant were measured with enzyme-linked immunosorbent assays (ELISAs). The mRNA and protein expression of TLR3, TLR4, nuclear factor kappa B (NF-?B) and tumor necrosis factor receptor-associated factor-6 (TRAF-6) were detected by real-time PCR and western blot methods, respectively. The experimental results showed that A?25-35 could markedly raise the level of TNF-?, IFN-? and iNOS, and increase the expressions of mRNA and TLR3, TLR4, NF-?B and TRAF-6 protein in the NG108-15 cells. At the same time, the ginsenoside Rg1 significantly reduced the expressions of proteins and mRNA of TLR3, TLR4, NF-?B and TRAF-6, and down-regulated the levels of TNF-?, IFN-? of cell supernatant and iNOS of cell lysate supernatant in a concentration-dependent manner. In conclusion, ginsenoside Rg1 has good activity for suppressing the signaling transduction pathway of TLR3 and TLR4, and decreasing the inflammation factors induced by A?25-35 in NG108-15 cells, and this may be the mechanism of ginsenoside Rg1 action in AD treatment, but more studies are needed to identify its specificity.
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Parameter estimation of dynamic biological network models using integrated fluxes.
BMC Syst Biol
PUBLISHED: 08-07-2014
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BackgroundParameter estimation is often the bottlenecking step in biological system modeling. For ordinary differential equation (ODE) models, the challenge in this estimation has been attributed to not only the lack of parameter identifiability, but also computational issues such as finding globally optimal parameter estimates over highly multidimensional search space. Recent methods using incremental estimation approach could alleviate the computational difficulty by performing the parameter estimation one¿reaction¿at¿a¿time. However, incremental estimation strategies usually require data smoothing and are known to produce biased parameter estimates.ResultsIn this article, we presented a new parameter estimation method called integrated flux parameter estimation (IFPE). We employed the integral form of the ODE such that we could compute the integral of reaction fluxes from time¿series concentration data without data smoothing. Here, we formulated the parameter estimation as a nested optimization problem. In the outer optimization, we performed a minimization of model prediction errors over parameters associated with a subset of reactions labeled as independent. The dimension of the independent reaction subset was equal to the degrees of freedom in the calculation of integrated fluxes (IF) from concentration data. We selected the independent reactions such that given their IF values, the IFs of the remaining (dependent) reactions could be uniquely determined. Meanwhile, in the inner optimization, we estimated the model parameters associated with the dependent reactions, one¿reaction¿at¿a¿time, by minimizing the dependent IF prediction errors. We demonstrated the performance of the IFPE method using two case studies: a generalized mass action model of a branched pathway and a lin¿log ODE model of Lactococcus lactis glycolytic pathway.ConclusionsThe IFPE significantly outperformed standard simultaneous parameter estimation in terms of computational efficiency and scaling. In comparison to incremental parameter estimation (IPE) method, the IFPE produced parameter estimates with significantly lower bias and did not require time¿series data smoothing. The advantages of IFPE over the IPE however came at the cost of a small increase in the computational time.
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Extracellular biogenic nanomaterials inhibit pyoverdine production in Pseudomonas aeruginosa: a novel insight into impacts of metal(loid)s on environmental bacteria.
Appl. Microbiol. Biotechnol.
PUBLISHED: 08-06-2014
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Anthropogenic activities such as mining, smelting, and industrial use have caused serious problems of metal(loid) pollution in nearly every country in the world. A wide range of environmental microorganisms are capable of transforming metal(loid)s into nanomaterials, i.e., biogenic nanomaterials (bio-NMs), in the environment. Although the impacts of various metal(loid)s on the ecosystems have been extensively studied, the potential influence of the bio-NMs generated in the environment to environmental organisms is largely unexplored. Using tellurium nanomaterials transformed from tellurite by a metal-reducing bacterium as model bio-NMs, we demonstrated that the bio-NMs significantly decreased siderophore production in an environmental bacterium Pseudomonas aeruginosa in both planktonic cultures and biofilms. Transcriptomic analysis revealed that the bio-NMs inhibited the expression of genes involved in biosynthesis and transport of siderophores. Siderophores secreted by certain bacteria in microbial communities can be considered as public goods that can be exploited by local communities, playing an important role in shaping microbial communities. The inhibition of siderophore production by the bio-NMs implies that bio-NMs may have an important influence on the ecosystems through altering specific functions of environmental bacteria. Taken together, this study provides a novel insight into the environmental impacts of metal(loid)s.
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A school-based study of irritable bowel syndrome in medical students in beijing, china: prevalence and some related factors.
Gastroenterol Res Pract
PUBLISHED: 08-04-2014
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Purpose. To investigate the prevalence and some related factors about irritable bowel syndrome (IBS) in medical students. Methods. A cross-sectional study was carried out from February 2014 to Jun 2014 in Beijing University of Chinese Medicine, Beijing, China. All participants were asked to completed self-administered questionnaires. Results. Seven hundred and sixty-seven medical students (23.26 ± 2.88 years, 25.6% males) completed the survey. The prevalence of IBS was 33.3%, with a high prevalence in women (36.1%). Among the IBS patients, 112 cases were IBS-M (43.9%) and 77.6% had moderately severe IBS. There were no statistical differences between control group and IBS patients in anxiety and depression scores (P > 0.05). The total score of Pittsburgh sleep quality index (PSQI) was significantly higher for medical students with IBS and 35.5% of IBS patients had severe sleep disorder; the scores of child trauma questionnaire (CTQ) and student-life stress inventory (SLSI) were also higher in IBS patients. Sex and sleep disorder were independently associated with IBS (OR, 1.914, 95%CI, 1.281-2.860; OR, 1.143, 95%CI, 1.074-1.216). Conclusion. Our study has many valuable findings and they may provide valuable suggestions for the necessary intervention and treatment measures towards medical students.
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Muscarinic M1 Receptors Regulate Propofol Modulation of GABAergic Transmission in Rat Ventrolateral Preoptic Neurons.
J. Mol. Neurosci.
PUBLISHED: 08-03-2014
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GABAergic neurons within the ventrolateral preoptic area (VLPO) play an important role in sleep-wakefulness regulation. Propofol, a widely used systemic anesthetic, has lately been reported to excite noradrenaline (NA)-inhibited type of VLPO neurons. Present study tested if acetylcholine system takes part in the propofol modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat VLPO neurons using a conventional whole-cell patch clamp technique. Propofol reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that propofol acts presynaptically to decrease the probability of spontaneous GABA release. The propofol action on GABAergic mIPSC frequency was completely blocked by atropine, a nonselective muscarinic acetylcholine (mACh) receptor antagonist, and pirenzepine, a selective M1 receptor antagonist. These results suggest that propofol acts on M1 receptors on GABAergic nerve terminals projecting to VLPO neurons to inhibit spontaneous GABA release. The M1 receptor-mediated modulation of GABAergic transmission onto VLPO neurons may contribute to the regulation of loss of consciousness induced by propofol.
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From Antidiabetic to Antifungal: Discovery of Highly Potent Triazole-Thiazolidinedione Hybrids as Novel Antifungal Agents.
ChemMedChem
PUBLISHED: 07-29-2014
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In an attempt to discover a new generation of triazole antifungal agents, a series of triazole-thiazolidinedione hybrids were designed and synthesized by molecular hybridization of the antifungal agent fluconazole and rosiglitazone (an antidiabetic). Most of the target compounds showed good to excellent inhibitory activity against a variety of clinically important fungal pathogens. In particular, compounds (Z)-5-(2,4-dichlorobenzylidene)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)thiazolidine-2,4-dione) (15?c), (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15?j), and (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15?r) were highly active against Candida albicans, with MIC80 values in the range of 0.03-0.15??M. Moreover, compounds 15?j and 15?r were found to be effective against four fluconazole-resistant clinical isolates; these two compounds are particularly promising antifungal leads for further optimization. Molecular docking studies revealed that the hydrogen bonding interactions between thiazolidinedione and CYP51 from C.?albicans are important for antifungal activity. This study also demonstrates the effectiveness of molecular hybridization in antifungal drug discovery.
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Numerical analysis of an H1-Galerkin mixed finite element method for time fractional telegraph equation.
ScientificWorldJournal
PUBLISHED: 07-24-2014
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We discuss and analyze an H(1)-Galerkin mixed finite element (H(1)-GMFE) method to look for the numerical solution of time fractional telegraph equation. We introduce an auxiliary variable to reduce the original equation into lower-order coupled equations and then formulate an H(1)-GMFE scheme with two important variables. We discretize the Caputo time fractional derivatives using the finite difference methods and approximate the spatial direction by applying the H(1)-GMFE method. Based on the discussion on the theoretical error analysis in L(2)-norm for the scalar unknown and its gradient in one dimensional case, we obtain the optimal order of convergence in space-time direction. Further, we also derive the optimal error results for the scalar unknown in H(1)-norm. Moreover, we derive and analyze the stability of H(1)-GMFE scheme and give the results of a priori error estimates in two- or three-dimensional cases. In order to verify our theoretical analysis, we give some results of numerical calculation by using the Matlab procedure.
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A least square method based model for identifying protein complexes in protein-protein interaction network.
Biomed Res Int
PUBLISHED: 07-22-2014
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Protein complex formed by a group of physical interacting proteins plays a crucial role in cell activities. Great effort has been made to computationally identify protein complexes from protein-protein interaction (PPI) network. However, the accuracy of the prediction is still far from being satisfactory, because the topological structures of protein complexes in the PPI network are too complicated. This paper proposes a novel optimization framework to detect complexes from PPI network, named PLSMC. The method is on the basis of the fact that if two proteins are in a common complex, they are likely to be interacting. PLSMC employs this relation to determine complexes by a penalized least squares method. PLSMC is applied to several public yeast PPI networks, and compared with several state-of-the-art methods. The results indicate that PLSMC outperforms other methods. In particular, complexes predicted by PLSMC can match known complexes with a higher accuracy than other methods. Furthermore, the predicted complexes have high functional homogeneity.
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Enhanced production of botrallin and TMC-264 with in situ macroporous resin adsorption in mycelial liquid culture of the endophytic fungus Hyalodendriella sp. Ponipodef12.
Molecules
PUBLISHED: 07-22-2014
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Hyalodendriella sp. Ponipodef12, an endophytic fungus from the hybrid "Neva" of Populus deltoides × P. nigra, is a high producer of the bioactive dibenzo-?-pyrones botrallin and TMC-264. However, both the botrallin and TMC-264 produced by Hyalodendriella sp. Ponipodef12 were retained as both intracellular and extracellular products. The aim of this study was to evaluate an in situ macroporous resin adsorption for enhancement of botrallin and TMC-264 production in mycelial liquid culture of Hyalodendriella sp. Ponipodef12. Production of botrallin and TMC-264 was most effectively enhanced by macroporous resin DM-301 among the thirteen nonionic macroporous resins tested. The highest botrallin yield (51.47 mg/L, which was 2.29-fold higher than the control at 22.49 mg/L) was obtained by adding resin DM-301 at 4.38% (g/mL) to the culture broth on day 24 and allowing a period of 4 days for adsorption. The highest TMC-264 yield reached 47.74 mg/L, which was 11.76-fold higher than that of the control (4.06 mg/L), and was achieved by adding DM-301 resin at 4.38% (w/v) in the culture broth on day 24 and allowing a period of 6 days for adsorption. The results show that in situ resin adsorption is an effective strategy for enhancing production of botrallin and TMC-264, and also for facilitating their recovery from mycelial liquid culture of Hyalodendriella sp. Ponipodef12.
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Clinical evaluation of the Asian proximal femur intramedullary nail antirotation system (PFNA-II) for treatment of intertrochanteric fractures.
J Orthop Surg Res
PUBLISHED: 07-20-2014
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BackgroundThe preferred treatment of intertrochanteric fractures in aged patients is controversial. The purpose of the present study was to evaluate the outcomes of the Asian proximal femur intramedullary nail antirotation system (PFNA-II) for stabilization of such fractures.MethodsThe PFNA-II was used to treat intertrochanteric fractures in 163 elderly patients from March 2010 to March 2013. The patients comprised 69 men and 94 women with a mean age of 74.7¿±¿13.0 years. All fractures were classified by the Orthopaedic Trauma Association classification system; 53, 83, and 27 fractures were classified as 31A1, 31A2, and 31A3, respectively. We statistically evaluated the intraoperative blood loss, operation time, incision length, X-ray exposure time, and postoperative outcomes. Patients were followed up for a mean of 15.2 months (range, 10¿24 months). Functional outcomes were assessed according to the Harris hip scoring system.ResultsStatistical analysis revealed an average operation time of 45.7 min (range, 35¿110 min), average intraoperative blood loss of 115.2 mL (range, 65¿430 mL), X-ray exposure time of 2.7¿±¿1.4 s (range, 2¿6 s), and total incision length of 6.5¿±¿2.2 cm (range, 5.5¿13.0 cm). Patients were followed up for a mean of 14.5 months (range, 10¿24 months). The neck shaft angle was 134° ±15° (range, 115°¿150°), and the fracture healing time was 14.0¿±¿2.5 weeks (range, 11¿19 weeks). The Harris hip score was 85.6¿±¿17.5 points (range, 65¿100 points) and included 41 excellent cases (25.15%), 92 good cases (56.44%), 26 moderate cases (15.95%), and 4 poor cases (2.45%) for a positive outcome rate of 81.60%. There were no varus hip deformities, screw cutouts, or femoral shaft fractures. Fourteen patients had thigh pain (9.82%), and five had inner thigh pain (3.07%); seven had more severe pain that was improved by physical therapy.ConclusionPFNA-II has the advantages of a simple operation, few complications, and clinical efficacy for the treatment of intertrochanteric fractures. However, evaluation of its long-term efficacy and risk of other complications requires a large-sample, multicenter observational study.
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