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Find video protocols related to scientific articles indexed in Pubmed.
Enhancement of the field emission from the TiO2 nanotube arrays by reducing in a NaBH4 solution.
ACS Appl Mater Interfaces
PUBLISHED: 11-20-2014
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A mass of oxygen vacancies are successfully introduced into TiO2 nanotube arrays using low-cost NaBH4 as a reductant in a liquid-phase environment. By controlling and adjusting the reduction time over the range of 0-24 h, the doping concentration of the oxygen vacancy realizes controllable and eventually reaches saturation. Meanwhile, the thermal stability of oxygen vacancies is also investigated, indicating that part of oxygen vacancies remain stable up to 250 °C. In addition, this liquid-phase reduction strategy significantly lowers the requirements of instruments and cost. More interesting, reduced TiO2 nanotube arrays show drastically enhanced field emission performances including substantially decreased turn-on field from 25.01 to 2.65 V/?m, a high current density of 3.5 mA/cm2 at 7.2 V/?m and an excellent field emission stability and repeatability. These results are attributed to the oxygen vacancies obtained by reducing in NaBH4 solution, resulting in a reduced effective work function and an increased conductivity.
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One-way transmission of 10 Gbps data through a silicon optical diode based on nonreciprocal resonance reshaping.
Opt Express
PUBLISHED: 11-18-2014
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The reduced optical bandwidth associated with resonance enhancement poses a significant challenge for resonators to process wide-bandwidth optical data. We report one-way transmission of 10 giga-bit-per-second optical data through a silicon optical diode based on both the resonance-enhanced optical nonlinear effects and resonance reshaping. The diode is operated with a forward-only or backward-only input. In the backward direction, the diode corrupts the data through the strong dispersion and attenuation associated with the resonance of a microring. In the forward direction, the data pass through the diode with negligible distortions because the resonance is red-shifted from the carrier wavelength. In this experimental context the finite bandwidth associated with the optical resonance may be considered beneficial, since the phase response makes an additional contribution to transmission nonreciprocity beyond what is seen with unmodulated light.
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The genome of a Mongolian individual reveals the genetic imprints of Mongolians on modern human populations.
Genome Biol Evol
PUBLISHED: 11-08-2014
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Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162?-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions (Indels). Functional SNP analysis predicted the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13(th) century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians.
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Impact of chemotherapy-related hyperglycemia on prognosis of child acute lymphocytic leukemia.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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To investigate the impact of hyperglycemia during inductive treatment on the prognosis of acute lymphocytic leukemia (ALL) in children.
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Phylogenomics resolves the timing and pattern of insect evolution.
Bernhard Misof, Shanlin Liu, Karen Meusemann, Ralph S Peters, Alexander Donath, Christoph Mayer, Paul B Frandsen, Jessica Ware, Tomáš Flouri, Rolf G Beutel, Oliver Niehuis, Malte Petersen, Fernando Izquierdo-Carrasco, Torsten Wappler, Jes Rust, Andre J Aberer, Ulrike Aspöck, Horst Aspöck, Daniela Bartel, Alexander Blanke, Simon Berger, Alexander Böhm, Thomas R Buckley, Brett Calcott, Junqing Chen, Frank Friedrich, Makiko Fukui, Mari Fujita, Carola Greve, Peter Grobe, Shengchang Gu, Ying Huang, Lars S Jermiin, Akito Y Kawahara, Lars Krogmann, Martin Kubiak, Robert Lanfear, Harald Letsch, Yiyuan Li, Zhenyu Li, Jiguang Li, Haorong Lu, Ryuichiro Machida, Yuta Mashimo, Pashalia Kapli, Duane D McKenna, Guanliang Meng, Yasutaka Nakagaki, José Luis Navarrete-Heredia, Michael Ott, Yanxiang Ou, Günther Pass, Lars Podsiadlowski, Hans Pohl, Björn M von Reumont, Kai Schütte, Kaoru Sekiya, Shota Shimizu, Adam Slipinski, Alexandros Stamatakis, Wenhui Song, Xu Su, Nikolaus U Szucsich, Meihua Tan, Xuemei Tan, Min Tang, Jingbo Tang, Gerald Timelthaler, Shigekazu Tomizuka, Michelle Trautwein, Xiaoli Tong, Toshiki Uchifune, Manfred G Walzl, Brian M Wiegmann, Jeanne Wilbrandt, Benjamin Wipfler, Thomas K F Wong, Qiong Wu, Gengxiong Wu, Yinlong Xie, Shenzhou Yang, Qing Yang, David K Yeates, Kazunori Yoshizawa, Qing Zhang, Rui Zhang, Wenwei Zhang, Yunhui Zhang, Jing Zhao, Chengran Zhou, Lili Zhou, Tanja Ziesmann, Shijie Zou, Yingrui Li, Xun Xu, Yong Zhang, Huanming Yang, Jian Wang, Jun Wang, Karl M Kjer, Xin Zhou.
Science
PUBLISHED: 11-06-2014
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Insects are the most speciose group of animals, but the phylogenetic relationships of many major lineages remain unresolved. We inferred the phylogeny of insects from 1478 protein-coding genes. Phylogenomic analyses of nucleotide and amino acid sequences, with site-specific nucleotide or domain-specific amino acid substitution models, produced statistically robust and congruent results resolving previously controversial phylogenetic relations hips. We dated the origin of insects to the Early Ordovician [~479 million years ago (Ma)], of insect flight to the Early Devonian (~406 Ma), of major extant lineages to the Mississippian (~345 Ma), and the major diversification of holometabolous insects to the Early Cretaceous. Our phylogenomic study provides a comprehensive reliable scaffold for future comparative analyses of evolutionary innovations among insects.
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Interactome Map Reveals Phospholipid Scramblase 1 as a Novel Regulator of Hepatitis B Virus X Protein.
J. Proteome Res.
PUBLISHED: 11-04-2014
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HBV X protein plays crucial roles during viral infection and hepatocellular carcinoma (HCC) development through interaction with various host factors. Here, we mapped the interactome of HBx using a yeast two-hybrid screen. Nine human proteins were identified as novel interacting partners of HBx, one of which is phospholipid scramblase 1 (PLSCR1). PLSCR1 is an interferon-inducible protein that mediates antiviral activity against DNA and RNA viruses. However, the molecular mechanisms of PLSCR1 activity against HBV remain unclear. Here, we reported that PLSCR1 promotes HBx degradation by a proteasome- and ubiquitin-dependent mechanism. Furthermore, we found that PLSCR1 inhibits HBx-mediated cell proliferation. After HBV infection, the protein level of PLSCR1 in plasma is elevated, and chronic hepatitis B patients with low plasma levels of PLSCR1 have a high risk of developing HCC. These results suggest that the nuclear trafficking of PLSCR1 mediates the antiviral activity and anticarcinogenesis against HBV by regulating HBx stability.
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Development of a computerized tool for the chinese version of the montreal cognitive assessment for screening mild cognitive impairment.
Int Psychogeriatr
PUBLISHED: 11-04-2014
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ABSTRACT Background: The Montreal Cognitive Assessment (MoCA) is used for screening mild cognitive impairment (MCI), and the Beijing version (MoCA-BJ) is widely used in China. We aimed to develop a computerized tool for MoCA-BJ (MoCA-CC). Methods: MoCA-CC used person-machine interaction instead of patient-to-physician interaction; other aspects such as the scoring system did not differ from the original test. MoCA-CC, MoCA-BJ and routine neuropsychological tests were administered to 181 elderly participants (MCI = 96, normal controls [NC] = 85). Results: A total of 176 (97.24%) participants were evaluated successfully by MoCA-CC. Cronbach's ? for MoCA-CC was 0.72. The test-retest reliability (retesting after six weeks) was good (intraclass correlation coefficient = 0.82; P < 0.001). Significant differences were observed in total scores (t = 9.38, P < 0.001) and individual item scores (t = 2.18-8.62, P < 0.05) between the NC and MCI groups, except for the score for "Naming" (t = 0.24, P = 0.81). The MoCA-CC total scores were highly correlated with the MoCA-BJ total scores (r = 0.93, P < 0.001) in the MCI participants. The area under receiver-operator curve for the prediction of MCI was 0.97 (95% confidence interval = 0.95-1.00). At the optimal cut-off score of 25/26, MoCA-CC demonstrated 95.8% sensitivity and 87.1% specificity. Conclusion: The MoCA-CC tool developed here has several advantages over the paper-pencil method and is reliable for screening MCI in elderly Chinese individuals, especially in the primary clinical setting. It needs to be validated in other diverse and larger populations.
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Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation.
J. Exp. Med.
PUBLISHED: 11-03-2014
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Influenza in humans is often accompanied by gastroenteritis-like symptoms such as diarrhea, but the underlying mechanism is not yet understood. We explored the occurrence of gastroenteritis-like symptoms using a mouse model of respiratory influenza infection. We found that respiratory influenza infection caused intestinal injury when lung injury occurred, which was not due to direct intestinal viral infection. Influenza infection altered the intestinal microbiota composition, which was mediated by IFN-? produced by lung-derived CCR9(+)CD4(+) T cells recruited into the small intestine. Th17 cells markedly increased in the small intestine after PR8 infection, and neutralizing IL-17A reduced intestinal injury. Moreover, antibiotic depletion of intestinal microbiota reduced IL-17A production and attenuated influenza-caused intestinal injury. Further study showed that the alteration of intestinal microbiota significantly stimulated IL-15 production from intestinal epithelial cells, which subsequently promoted Th17 cell polarization in the small intestine in situ. Thus, our findings provide new insights into an undescribed mechanism by which respiratory influenza infection causes intestinal disease.
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Identification of Two Novel Mutations in Patients With X-Linked Primary Immunodeficiencies.
Fetal Pediatr Pathol
PUBLISHED: 10-30-2014
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Primary immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders with defects in one or more component of the immune system. In this study, we analyzed gene mutations in four X-linked PID pedigrees, which include one X- linked agammaglobulinemia (XLA) pedigree, one X-linked chronic granulomatous disease (XCGD) pedigree, and two X-linked Hyper IgM syndrome (XHIGM) pedigrees. Sequence analysis of the BTK gene revealed a novel mutation (c.1802_1803delinsGCC, p.Phe601CysfsX3) which results in the developmental arrest of B cells in the bone marrow. Sequence analysis of the CYBB gene revealed a recurrent frameshift mutation (c.1313_1314delinsT) in exon 10, which generates a premature stop codon (p.Lys438IlefsX63). One novel frameshift mutation (c.114delG, p.Ser39GlnfsX14) and one recurrent missense mutation (c.499G>C, p.Gly167Arg) were found in the CD40LG gene and cause defective T cell functioning. In conclusion, our study identified two novel mutations on the BTK and CD40LG genes in Chinese patients and established accurate and simple genetic diagnostic methods for three X-linked PID.
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Properties of Fe-Organic Matter Associations via Coprecipitation versus Adsorption.
Environ. Sci. Technol.
PUBLISHED: 10-29-2014
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The association of organic matter (OM) with minerals is recognized as the most important stabilization mechanism for soil organic matter. This study compared the properties of Fe-OM complexes formed from adsorption (reaction of OM to postsynthesis ferrihydrite) versus coprecipitation (formation of Fe solids in the presence of OM). Coprecipitates and adsorption complexes were synthesized using dissolved organic matter (DOM) extracts from a forest little layer at varying molar C/Fe ratios of 0.3-25.0. Sample properties were studied by N2 gas adsorption, XRD, FTIR, Fe EXAFS, and STXM-NEXAFS techniques. Coprecipitation resulted in much higher maximum C contents (?130 mg g(-1) C difference) in the solid products than adsorption, which may be related to the formation of precipitated insoluble Fe(III)-organic complexes at high C/Fe ratios in the coprecipitates as revealed by Fe EXAFS analysis. Coprecipitation led to a complete blockage of mineral surface sites and pores with ?177 mg g(-1) C and molar C/Fe ratios ?2.8 in the solid products. FTIR and STXM-NEXAFS showed that the coprecipitated OM was similar in composition to the adsorbed OM. An enrichment of aromatic C was observed at low C/Fe ratios. Association of carboxyl functional groups with Fe was shown with FTIR and STXM-NEXAFS analysis. STXM-NEXAFS analysis showed a continuous C distribution on minerals. Desorption of the coprecipitated OM was less than that of the adsorbed OM at comparable C/Fe ratios. These results are helpful to understand C and Fe cycling in the natural environments with periodically fluctuating redox conditions, where coprecipitation can occur.
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Three-dimensional proton magnetic resonance spectroscopic imaging with and without an endorectal coil: a prostate phantom study.
Acta Radiol
PUBLISHED: 10-29-2014
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Proton magnetic resonance spectroscopic imaging (MRSI) of the prostate has been used with only a combination of external surface coils. The quality of spectral fitting of the (choline?+?creatine)/citrate ([Cho?+?Cr]/Cit) ratio at different field strengths and different coils is important for quantitative/semi-quantitative diagnosis of prostate cancer.
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Distorted Phosphorus and Copper Square-Planar Layers in LaCu1+xP2 and LaCu4P3: Synthesis, Crystal Structure, and Physical Properties.
Inorg Chem
PUBLISHED: 10-28-2014
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Two new lanthanum copper phosphides, LaCu1+xP2 and LaCu4P3, were synthesized from elements. Their crystal structures were determined by means of single-crystal X-ray diffraction. LaCu1+xP2 crystallizes in a complex crystal structure, a derivative of the HfCuSi2 structure type, in the space group Cmmm (No. 65) with unit cell parameters of a = 5.564(3) Å, b = 19.96(1) Å, c = 5.563(3) Å, and Z = 8. Its crystal structure features disordered Cu2xP2 layers alternated with fully ordered PbO-like Cu2P2 layers. The Cu-P layers are separated by La counter-cations. The Cu2xP2 layers are composed of rectangular P4 polyphosphide rings connected by partially occupied Cu atoms. Investigations of the electrical resistivity and Seebeck thermopower for LaCu1+xP2 reveal metallic-type behavior with holes as the main charge carriers. LaCu1+xP2 exhibits unexpectedly low thermal conductivity presumably because of disorder in the Cu2xP2 layers. LaCu4P3 crystallizes in a new structure type, in the tetragonal space group P4/nmm (No. 129) with unit cell parameters of a = 5.788(2) Å, c = 7.353(2) Å, and Z = 2. Its crystal structure features distorted square nets of Cu atoms within the Cu4P3 slabs. Electron localization function analysis indicates that both P atoms in LaCu4P3 have 1 + 4 coordination involving multicenter Cu-P bonding. According to the density of states and band structure, LaCu4P3 is predicted to be a metallic conductor.
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Discovery of Dual Leucine Zipper Kinase (DLK, MAP3K12) Inhibitors with Activity in Neurodegeneration Models.
J. Med. Chem.
PUBLISHED: 10-24-2014
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Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding mode and specific design parameters to optimize for CNS druglike molecules, we came to focus on the di(pyridin-2-yl)amines because of their combination of desirable potency and good brain penetration following oral dosing. Our lead inhibitor GNE-3511 (26) displayed concentration-dependent protection of neurons from degeneration in vitro and demonstrated dose-dependent activity in two different animal models of disease. These results suggest that specific pharmacological inhibition of DLK may have therapeutic potential in multiple indications.
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[Extracellular HMGB1 Promotes the Migration of Cord Blood CD34(+) Cells via SDF-1/CXCR-4 Axis].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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This study was aimed to investigate the effect of high mobility group box1(HMGB1) and/or stromal cell derived factor-1(SDF-1) on the migration of cord blood CD34(+) cells, and to explore whether HMGB1 promotes cord blood CD34(+) cell migration via SDF-1/CXCR4 axis. Cord blood mononuclear cells were isolated by Ficoll-Paque density centrifugation, CD34(+) cells were collected by a positive immunoselection procedure (CD34 MicroBeads) according to the manufacturer's instructions, the purity of the isolated CD34(+) cells was detected by flow cytometry. In vitro chemotaxis assays were performed using Transwell cell chambers to detect cells migration. 1×10(5) cells/well cord blood CD34(+) cells were added into the upper chambers. Different concentrations of HMGB1 and/or SDF-1 (0, 10, 25, 50, 100, 200 ng/ml) were used to detect the optimal concentrations of HMGB1 and/or SDF-1 for inducing migration of cord blood CD34(+) cells. Freshly isolated cord blood CD34(+) cells express CXCR4 (SDF-1 receptor), and HMGB1 receptor TLR-2,TLR-4 and RAGE. To explore which receptors were required for the synergy of HGMB1 and/or SDF-1 on cells migration, the anti-SDF-1, anti-CXCR4 and anti-RAGE antibodies were used to detect the effect of HGMB1 alone or with SDF-1 on cord blood CD34(+) cells migration. The results showed that the purity of CD34(+) cells isolated from cord blood mononuclear cells by magnetic cell sorting was 97.40 ± 1.26%, the 25 ng/ml SDF-1 did not induce migration of cord blood CD34(+) cells, whereas the optimal migration was observed at 100 ng/ml. HMGB1 alone did not induce migration up to 100 ng/ml. The dose test found that the the best synergistic concentrations for cells migration were 100 ng/ml HMGB1 combined with 50 ng/ml SDF-1. The blocking test showed that both the anti-SDF-1 (4 µg/ml) and anti-CXCR4 (5 µg/ml) antibodies could block cell migration induced by HMGB1 or combined with SDF-1, but the cord blood CD34(+) cells in the presence of anti-RAGE, anti-TLR-2 and anti-TLR-4 antibodies did not modify the response to SDF-1 in the presence of HMGB1. It is concluded that both HMGB1 and SDF-1 can induce cord blood CD34(+) cells migration, HMGB1 enhances SDF-1-induced migration exclusively via CXCR4 and in a RAGE and TLR receptors-independent manner, the exact mechanism needs to be further explored.
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Integrating PPI datasets with the PPI data from biomedical literature for protein complex detection.
BMC Med Genomics
PUBLISHED: 10-22-2014
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Protein complexes are important for understanding principles of cellular organization and function. High-throughput experimental techniques have produced a large amount of protein-protein interactions (PPIs), making it possible to predict protein complexes from protein-protein interaction networks. On the other hand, the rapidly growing biomedical literature provides a significantly large and readily available source of interaction data, which can be integrated into the protein network for better complex detection performance.
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Predicting protein complex in protein interaction network - a supervised learning based method.
BMC Syst Biol
PUBLISHED: 10-22-2014
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Protein complexes are important for understanding principles of cellular organization and function. High-throughput experimental techniques have produced a large amount of protein interactions, making it possible to predict protein complexes from protein -protein interaction networks. However, most of current methods are unsupervised learning based methods which can't utilize the information of the large amount of available known complexes.
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Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder.
Brain
PUBLISHED: 10-22-2014
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Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson's disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. (18)F-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0 ± 5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5 ± 7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6 ± 5.0 years) and 16 moderate parkinsonian patients (age 56.9 ± 12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network characterized by increased activity in pons, thalamus, medial frontal and sensorimotor areas, hippocampus, supramarginal and inferior temporal gyri, and posterior cerebellum, with decreased activity in occipital and superior temporal regions. Compared to the healthy control subjects, network expressions were elevated (P < 0.0001) in the patients with this disorder and in the parkinsonian cohorts but decreased with disease progression. Parkinson's disease-related network activity was also elevated (P < 0.0001) in the patients with rapid eye movement sleep behaviour disorder but lower than in the hemi-parkinsonian cohort. Abnormal metabolic networks may provide markers of idiopathic rapid eye movement sleep behaviour disorder to identify those at higher risk to develop neurodegenerative parkinsonism.
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Uchl1 and its associated proteins were involved in spermatocyte apoptosis in mouse experimental cryptorchidism.
Sheng Li Xue Bao
PUBLISHED: 10-22-2014
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Uchl1 was found to be involved in spermatocyte apoptosis. The aim of the present study was to test whether Uchl1 and its associated proteins Jab1 and p27(kip1) were involved in spermatogenic damages in response to heat-stress in cryptorchidism. Hematoxylin and eosin (HE) staining and DNA end labeling (TUNEL) were used to observe morphological and apoptotic characteristics of spermatogenic cells; Immunohistochemical analysis was used to detect changes of Uchl1 and its associated proteins Jab1 and p27(kip1) in response to heat-stress from cryptorchidism leading to spermatocyte losses; And protein affinity analysis (pull-down) and immunofluorescence co-localization were used to verify the relevance among the three proteins in spermatocytes. The results showed that, Jab1 and p27(kip1), in parallel to Uchl1, increased in spermatocytes of apoptotic appearances in response to heat-stress, but not in multinucleated giant cells; Jab1 bound to Uchl1 in testis protein extracts, and co-localized with Uchl1 and p27(kip1) specifically in spermatocytes with apoptotic appearances. These results suggest that the accumulation of Uchl1 protein is involved in the heat-stress-induced spermatocyte apoptosis through a new pathway related with Jab1 and p27(kip1), but not the formation of multinucleated giant cells.
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Plasmonic hybridization induced trapping and manipulation of a single au nanowire on a metallic surface.
Nano Lett.
PUBLISHED: 10-21-2014
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Hybridization in the narrow gaps between the surface plasmon polaritons (SPPs) along a metal surface and the localized surface plasmons on metallic nano-objects strongly enhance the electromagnetic field. Here, we employ plasmonic hybridization to achieve dynamic trapping and manipulation of a single metallic nanowire on a flat metal surface. We reveal that the plasmonic hybridization achieved by exciting plasmonic tweezers with a linearly polarized laser beam could induce strong trapping forces and large rotational torques on a single metallic nanowire. The position and orientation of the nanowire could dynamically be controlled by the hybridization-enhanced nonisotropic electric field in the gap. Experimental results further verify that a single Au nanowire could robustly be trapped at the center of an excited SPP field by the induced forces and then rotated by the torques. Finally, a plasmonic swallow tail structure is built to demonstrate its potential in the fabrication of lab-on-a-chip plasmonic devices.
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Optical data exchange of m-QAM signals using a silicon-organic hybrid slot waveguide: proposal and simulation.
Opt Express
PUBLISHED: 10-17-2014
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We present modulation-format-transparent data exchange for m-ary quadrature amplitude modulation (m-QAM) signals using a single silicon-organic hybrid slot waveguide which offers tight light confinement and enhanced nonlinearity. By exploiting the parametric depletion effect of non-degenerate four-wave mixing (ND-FWM) process in the slot waveguide, we simulate low-power (<10 mW) ultrahigh-speed optical data exchange of 640 Gbaud (2.56 Tbit/s) optical time-division multiplexed (OTDM) 16-QAM and 640 Gbaud (3.84 Tbit/s) OTDM 64-QAM signals and characterize the operation performance in terms of error vector magnitude (EVM) and bit-error rate (BER). The calculated signal-to-noise ratio (SNR) penalties of data exchange are negligible for 2.56 Tbit/s 16-QAM signals and less than 2 dB for 3.84 Tbit/s 64-QAM signals at a BER of 2e-3. For a given pump power of 9 mW, the operation performance dependence on the waveguide length is studied, showing an optimized waveguide length of ~17 mm. For a given waveguide length of 17 mm, the SNR penalty of data exchange, at a BER of 2e-3, is kept below 4 dB when varying input pump power from 8.4 to 9.8 mW for 2.56 Tbit/s 16-QAM and from 8.9 to 9.2 mW for 3.84 Tbit/s 64-QAM. In addition, data exchange running at low speed (e.g. 20 Gbaud) and data exchange taking into account waveguide propagation loss are also analyzed with favorable operation performance.
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The effects of hypotonic and isotonic negative contrast agent on gastrointestinal distention and physiological intake of 18F-FDG.
Nucl Med Commun
PUBLISHED: 10-17-2014
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The objective of this study was to explore the effects of hypotonic and isotonic oral mannitol on intestinal distention and fluorine-18 fluorodeoxyglucose (F-FDG) intake in PET/computed tomography (CT) imaging.
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Postsynaptic insertion of AMPA receptor onto cortical pyramidal neurons in the anterior cingulate cortex after peripheral nerve injury.
Mol Brain
PUBLISHED: 10-07-2014
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Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. Postsynaptic accumulation of AMPA receptor (AMPAR) GluA1 plays an important role for injury-related cortical LTP. However, there is no direct evidence for postsynaptic GluA1 insertion or accumulation after peripheral injury. Here we report nerve injury increased the postsynaptic expression of AMPAR GluA1 in pyramidal neurons in the layer V of the anterior cingulate cortex (ACC), including the corticospinal projecting neurons. Electrophysiological recordings show that potentiation of postsynaptic responses was reversed by Ca2+ permeable AMPAR antagonist NASPM. Finally, behavioral studies show that microinjection of NASPM into the ACC inhibited behavioral sensitization caused by nerve injury. Our findings provide direct evidence that peripheral nerve injury induces postsynaptic GluA1 accumulation in cingulate cortical neurons, and inhibits postsynaptic GluA1 accumulation which may serve as a novel target for treating neuropathic pain.
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Flush-mounted probe diagnostics for argon glow discharge plasma.
Rev Sci Instrum
PUBLISHED: 10-03-2014
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A comparison is made between plasma parameters measured by a flush-mounted probe (FP) and a cylindrical probe (CP) in argon glow discharge plasma. Parameters compared include the space potential, the plasma density, and the effective electron temperature. It is found that the ion density determined by the FP agrees well with the electron density determined by the CP in the quasi-neutral plasma to better than 10%. Moreover, the space potential and effective electron temperature calculated from electron energy distribution function measured by the FP is consistent with that measured by the CP over the operated discharge current and pressure ranges. These results present the FP can be used as a reliable diagnostic tool in the stable laboratory plasma and also be anticipated to be applied in other complicated plasmas, such as tokamaks, the region of boundary-layer, and so on.
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[A meta-analysis of esophagectomy: the comparative study of Ivor-Lewis operation and Sweet operation].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 10-03-2014
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Investigate the best surgical resection of esophageal cancer by comparing the efficacy and safety between Ivor-Lewis esophagectomy and Sweet esophagectomy.
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Ultrahigh-Performance Liquid Chromatography Electrospray Ionization Q-Orbitrap Mass Spectrometry for the Analysis of 451 Pesticide Residues in Fruits and Vegetables: Method Development and Validation.
J. Agric. Food Chem.
PUBLISHED: 09-30-2014
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This paper presents an application of ultrahigh-performance liquid chromatography electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC/ESI Q-Orbitrap MS) for the determination of 451 pesticide residues in fruits and vegetables. Pesticides were extracted from samples using the QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure. UHPLC/ESI Q-Orbitrap MS in full MS scan mode acquired full MS data for quantification, and UHPLC/ESI Q-Orbitrap Full MS/dd-MS(2) (i.e., data-dependent scan mode) obtained product ion spectra for identification. UHPLC/ESI Q-Orbitrap MS quantification was achieved using matrix-matched standard calibration curves along with the use of isotopically labeled standards or a chemical analogue as internal standards to achieve optimal method accuracy. The method performance characteristics include overall recovery, intermediate precision, and measurement uncertainty evaluated according to a nested experimental design. For the 10 matrices studied, 94.5% of the pesticides in fruits and 90.7% in vegetables had recoveries between 81 and 110%; 99.3% of the pesticides in fruits and 99.1% of the pesticides in vegetables had an intermediate precision of ?20%; and 97.8% of the pesticides in fruits and 96.4% of the pesticides in vegetables showed measurement uncertainty of ?50%. Overall, the UHPLC/ESI Q-Orbitrap MS demonstrated acceptable performance for the quantification of pesticide residues in fruits and vegetables. The UHPLC/ESI Q-Orbitrap Full MS/dd-MS(2) along with library matching showed great potential for identification and is being investigated further for routine practice.
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Association between serum uric acid and mortality in a Chinese population of hypertensive patients.
Ren Fail
PUBLISHED: 09-27-2014
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Abstract Objectives: To investigate the association between serum uric acid and mortality in a Chinese population of hypertensive patients. Methods and results: A total of 2757 Chinese hypertensive patients from department of cardiology of several hospitals in Shanghai in China were followed up for about six years in this prospective study. Mortality was recorded and related factors were evaluated. Hyperuricemia was diagnosed by serum uric acid levels of >420?µmol/L in males or >357?µmol/L in females. A total of 2585 hypertensive patients with complete data were included in the final statistical analysis. Totally 709 deaths (27.4%) occurred during the six-year follow-up, of which 475 deaths were attributable to cardiovascular disease (CVD). All-cause and CVD mortality of hypertensive patients with hyperuricemia was significantly higher than that of patients without hyperuricemia. The Cox regression analysis indicated that hazards ratios (HRs) of hyperuricemia for all-cause and CVD mortality were 1.206 (95% CI: 1.002-1.453) and 1.085 (95% CI: 1.002-1.271) respectively. All-cause and CVD mortality of hypertensive patients was significantly increased (both p?536?µmol/L to all-cause and CVD mortality of hypertensive patients were 2.115 (95% CI: 1.596-2.801) and 1.861 (95% CI: 1.296-2.673), respectively, compared with those of uric acid levels ?357?µmol/L. Conclusions: The data from this cohort study indicate that hyperuricemia can predict increased all-cause and CVD mortality in hypertensive patients.
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Oxidative Enantioselective ?-Fluorination of Aliphatic Aldehydes Enabled by N-Heterocyclic Carbene Catalysis.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 09-25-2014
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Described is the first study on oxidative enantioselective ?-fluorination of simple aliphatic aldehydes enabled by N-heterocyclic carbene catalysis. N-fluorobis(phenyl)sulfonimide serves as a an oxidant and as an "F" source. The C?F bond formation occurs directly at the ? position of simple aliphatic aldehydes, thus overcoming nontrivial challenges, such as competitive difluorination and nonfluorination, and proceeds with high to excellent enantioselectivities.
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Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm.
Arch. Pharm. Res.
PUBLISHED: 09-23-2014
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Baicalin, a flavonoid, has a wide range of pharmacological properties, including immunomodulation. The objective of this study was to investigate the effect of baicalin on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in a colitis model. The rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baicalin (10 ml/kg, each) or mesalazine (positive control) was then administered orally for 7 days. Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. Our study showed that baicalin not only significantly attenuated TNBS-induced colitis by reducing the disease activity index as well as macroscopic and microscopic scores, but it also improved the weight loss and shortening of the colon. Baicalin treatment also induced a significant decrease in the levels of inflammatory mediators, including the myeloperoxidase activity, the levels of tumor necrosis factor ?, IL-1?, and Th1-related cytokines IL-12 and IFN-?. Furthermore, the beneficial effects of baicalin seem to be associated with regulation of the Th17 and Treg paradigm. We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor ?t. In contrast, there was an increase in Treg cells numbers, Treg-related cytokines transforming growth factor-? and IL-10, and forkhead box P3. Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis.
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[Dental caries conditions of 3,439 disabled Yi and Han individuals in Liangshan Yi Autonomous Prefecture in Sichuan province, China].
Hua Xi Kou Qiang Yi Xue Za Zhi
PUBLISHED: 09-23-2014
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This study aims to conduct a survey of the oral health status of disabled individuals in Liangshan Autonomous Prefecture in Sichuan province. This study was also conducted to prepare caries prevention planning in the region.
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Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition.
Expert Opin Biol Ther
PUBLISHED: 09-19-2014
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Objective: Fetal placental mesenchymal stem cells (fPMSCs) have shown promising cell therapy potentials. However, their genetic and epigenetic stability during in vitro propagation has not been well studied. We thus interrogated the methylation alterations and tumorigenicity of fPMSCs after in vitro expansion using serum-free medium. Research design and methods: The properties of fPMSCs cultured in a serum-free medium at passage 3 and passage 8 were ascertained by determining their MSC markers, proliferative capacity, chromosomal stability, activity of global DNA methyltransferases and methylation profile. Their potential of malignant transformation was also evaluated in a severe combined immunodeficiency (SCID) murine model. Results: The fPMSCs could maintain their MSC characteristics but quickly reached a senescent state of proliferation during in vitro expansion. 246 genes with differential DNA methylation of promoters were identified, along with a significantly downregulated global DNA methyltransferase activity. The genes associated with aging and tumorigenesis had a significantly demethylated tendency over in vitro propagation. However, the deposition of epigenetic alterations did not translate into malignant transformation in SCID mice. Conclusion: The fPMSCs cultured in serum-free medium have a tendency to deposit methylation modifications over in vitro expansion, therefore the detection of genetic and/or epigenetic alterations is necessary for fPMSCs before they are employed for clinical uses.
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MixGF: spectral probabilities for mixture spectra from more than one peptide.
Mol. Cell Proteomics
PUBLISHED: 09-17-2014
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In large-scale proteomic experiments, multiple peptide precursors are often co-fragmented simultaneously in the same mixture tandem mass (MS/MS) spectrum. These spectra tend to elude current computational tools because of the ubiquitous assumption that each spectrum is generated from only one peptide. Therefore, tools that consider multiple peptide matches to each MS/MS spectrum can potentially improve the relatively low spectrum identification rate often observed in proteomics experiments. More importantly, data independent acquisition protocols \emph{promoting} the co-fragmentation of multiple precursors are emerging as alternative methods that can greatly improve the throughput of peptide identifications but their success also depends on the availability of algorithms to identify multiple peptides from each MS/MS spectrum. Here we address a fundamental question in the identification of mixture MS/MS spectra: determining the statistical significance of multiple peptides matched to a given MS/MS spectrum. We propose the MixGF generating function model to rigorously compute the statistical significance of peptide identifications for mixture spectra and show that this approach improves the sensitivity of current mixture spectra database search tools by a approximately 30% - 390%. Analysis of multiple datasets with MixGF reveals that in complex biological samples the number of identified mixture spectra can be as high as 20% of all the identified spectra and the number of unique peptides identified only in mixture spectra can be up to 35.4% of those identified in single-peptide spectra.
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[Research on the treatment of liver failure rats with transplantation of alginate microencapsulated hepatocytes in vivo based on poly-ornithine].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 09-16-2014
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This study aims to explore the effects of alginate-poly ornithine-alginate (A-PLO-A) and barium alginate-poly ornithine-alginate (B-PLO-A) microcapsules as cells carriers during implantation. Mice hepatocytes coated in A-PLO-A and B-PLO-A microcapsules were implanted into rats with acute liver failure caused by intraperitoneal injection of D-galactosamine. The rat survival rate, liver cell growth, proliferation and metabolism within the microcapsules were investigated, as well as its effect on the improvement of rat acute liver failure. The influence of A-PLO-A-free microcapsules, B-PLO-A-free microcapsules, isolated liver cells, A-PLO-A microcapsule-coated and B-PLO-A microcapsule-coated liver cells was studied. It was found that the chemical-free microcapsules showed no positive effect on the rats with liver failures, with a death rate of 100% in both groups 3 days after the implantation. The ALT, AST and ALB levels were all improved in the isolated liver cell group, the A-PLO-A microcapsule-coated and the B-PLO-A microcapsule-coated groups. The survival rate of both microcapsule-coated liver cell groups was significantly higher than that of the chemical-free microcapsule group and the isolated liver cells group. The microcapsules were retrieved after 4 weeks' implantation, which were observed to be smooth with no cells attaching to the surface. No apparent fibrosis was observed. This research demonstrated the physical stability and the biocompatibility of the PLO-based alginate microcapsules and therefore they could be used as liver cell carriers during implantation.
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Yersinia Protein Kinase A Phosphorylates Vasodilator-Stimulated Phosphoprotein to Modify the Host Cytoskeleton.
Cell. Microbiol.
PUBLISHED: 09-13-2014
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Pathogenic Yersinia species evolved a type III secretion system that injects a set of effectors into the host cell cytosol to promote infection. One of these effectors, Yersinia protein kinase A (YpkA), is a multidomain effector that harbors a Ser/Thr kinase domain and a guanine dissociation inhibitor (GDI) domain. The intercellular targets of the kinase and GDI domains of YpkA were identified to be G?q and the small GTPases RhoA and Rac1, respectively, which synergistically induce cytotoxic effects on infected cells. In this study, we demonstrate that vasodilator-stimulated phosphoprotein (VASP), which is critical for regulation of actin assembly, cell adhesion, and motility is a direct substrate of YpkA kinase activity. Ectopic coexpression of YpkA and VASP in HEK293T cells lead to the phosphorylation of VASP at S157, and YpkA kinase activity is essential for VASP phosphorylation at this site. Moreover, YpkA directly phosphorylates VASP in in vitro kinase assay. YpkA-mediated VASP phosphorylation significantly inhibits actin polymerization and promotes the disruption of actin cytoskeleton, which inhibits the phagocytosis. Taken together, our study found a novel molecular mechanism used by YpkA to disrupt cytoskeleton dynamics, thereby promoting the anti-phagocytosis ability of pathogenic Yersiniae.
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De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells.
Oncotarget
PUBLISHED: 09-13-2014
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The impact of cellular oxidative stress in promoting the epithelial-mesenchymal transition (EMT) has been noticed. Our previous study shows that SENP3, a redox-sensitive SUMO2/3-specific protease, accumulates in a variety of cancers, but whether SENP3 and SUMOylation involve in the regulation of EMT is unclear. The present study uncovers a novel role of SENP3 in promoting the EMT process in gastric cancer via regulating an EMT-inducing transcription factor, forkhead box C2 (FOXC2). We demonstrate that the expression of mesenchymal marker genes and cell migration ability are enhanced in SENP3-overexpressing gastric cancer cells and attenuated in SENP3-knockdown cells. A nude mouse model and a set of patient's specimens suggest the correlation between SENP3 and gastric cancer metastasis. Biochemical assays identify FOXC2 as a substrate of SENP3. Meanwhile N-cadherin is verified as a target gene of FOXC2, which is transcriptionally activated by a SUMO-less FOXC2. Additionally, reactive oxygen species-induced de-SUMOylation of FOXC2 can be blocked by silencing endogenous SENP3. In conclusion, SENP3, which is increased in gastric cancer cells, potentiates the transcriptional activity of FOXC2 through de-SUMOylation, in favor of the induction of specific mesenchymal gene expression in gastric cancer metastasis.
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Nano(Q)SAR: Challenges, pitfalls and perspectives.
Nanotoxicology
PUBLISHED: 09-12-2014
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Abstract Regulation for nanomaterials is urgently needed, and the drive to adopt an intelligent testing strategy is evident. Such a strategy will not only provide economic benefits but will also reduce moral and ethical concerns arising from animal testing. For regulatory purposes, such an approach is promoted by REACH, particularly the use of quantitative structure-activity relationships [(Q)SAR] as a tool for the categorisation of compounds according to their physicochemical and toxicological properties. In addition to compounds, (Q)SAR has also been applied to nanomaterials in the form of nano(Q)SAR. Although (Q)SAR in chemicals is well established, nano(Q)SAR is still in early stages of development and its successful uptake is far from reality. This article aims to identify some of the pitfalls and challenges associated with nano-(Q)SARs in relation to the categorisation of nanomaterials. Our findings show clear gaps in the research framework that must be addressed if we are to have reliable predictions from such models. Three major barriers were identified: the need to improve quality of experimental data in which the models are developed from, the need to have practical guidelines for the development of the nano(Q)SAR models and the need to standardise and harmonise activities for the purpose of regulation. Of these three, the first, i.e. the need to improve data quality requires immediate attention, as it underpins activities associated with the latter two. It should be noted that the usefulness of data in the context of nano-(Q)SAR modelling is not only about the quantity of data but also about the quality, consistency and accessibility of those data.
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[Primitive myxoid mesenchymal tumor of infancy: a clinicopathologic study of 3 additional cases].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 09-12-2014
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To study the clinicopathologic characteristics, immunophenotypes and differential diagnosis of primitive myxoid mesenchymal tumor of infancy (PMMTI).
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[Sarcomatoid malignant mesothelioma: a clinicopathologic and immunohistochemical analysis of 22 cases].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 09-12-2014
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To elaborate on the clinical and pathologic features of sarcomatoid malignant mesothelioma (SMM), its diagnostic criteria and differential diagnoses.
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[The value of multi-slice spiral computed tomography portography in assessing severity of liver cirrhosis and predicting episode risks of hepatic encephalopathy].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-10-2014
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To explore the clinical value of multi-slice spiral computed tomography portography (MSCTP) in assessing severity of liver cirrhosis and predicting episode risks of hepatic encephalopathy (HE).
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Parenteral Nutrition-Associated Liver Injury is Associated With Increased GRP94 Expression Prevented by Omega-3 Fish Oil-Based Lipid Emulsion Supplementation.
J. Pediatr. Gastroenterol. Nutr.
PUBLISHED: 09-09-2014
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Parenteral nutrition in infants with gastrointestinal orders can be lifesaving, but is also associated with parenteral nutrition-associated liver disease. We investigated the effects of incorporating omega-3 fish oil in a parenteral nutrition mixture on signs of parenteral nutrition-associated liver disease and explored the mechanism involved in this process.
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Gene function prediction based on the Gene Ontology hierarchical structure.
PLoS ONE
PUBLISHED: 09-05-2014
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The information of the Gene Ontology annotation is helpful in the explanation of life science phenomena, and can provide great support for the research of the biomedical field. The use of the Gene Ontology is gradually affecting the way people store and understand bioinformatic data. To facilitate the prediction of gene functions with the aid of text mining methods and existing resources, we transform it into a multi-label top-down classification problem and develop a method that uses the hierarchical relationships in the Gene Ontology structure to relieve the quantitative imbalance of positive and negative training samples. Meanwhile the method enhances the discriminating ability of classifiers by retaining and highlighting the key training samples. Additionally, the top-down classifier based on a tree structure takes the relationship of target classes into consideration and thus solves the incompatibility between the classification results and the Gene Ontology structure. Our experiment on the Gene Ontology annotation corpus achieves an F-value performance of 50.7% (precision: 52.7% recall: 48.9%). The experimental results demonstrate that when the size of training set is small, it can be expanded via topological propagation of associated documents between the parent and child nodes in the tree structure. The top-down classification model applies to the set of texts in an ontology structure or with a hierarchical relationship.
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Copper-catalyzed C(sp2)-H amidation with azides as amino sources.
Org. Lett.
PUBLISHED: 09-05-2014
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A copper-catalyzed C-H amidation process, with azides as amino sources under oxidant-free conditions, has been developed. When N-heterocycles were employed as directing groups, sulfonylazide and benzoylazide could be used as amidating reagents to provide corresponding N-arylamides. When amidines or imine were used, tandem C-N/N-N bond formation occurred to afford indazole derivatives in one pot.
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Survival of people living with HIV after treatment with traditional Chinese medicine in Henan province of China: a retrospective cohort study.
J Tradit Chin Med
PUBLISHED: 09-05-2014
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To provide survival estimates of people living with human immunodeficiency virus (PLHIV) after treatment with Traditional Chinese Medicine (TCM) in rural China, to identify the prognostic factors at enrollment, and to explore the effectiveness ofTCM in treating PLHIV.
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Smoking, smoking cessation and tobacco control in rural China: a qualitative study in Shandong Province.
BMC Public Health
PUBLISHED: 09-04-2014
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Smoking prevalence is high in China and even higher among rural residents. The aims of this study were: 1) to gain insights into the motivations of tobacco use and barriers to smoking cessation among rural village residents; 2) to understand the current tobacco control measures in the rural villages and barriers encountered or perceived for implementation.
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An 84-month observational study of the changes in CD4 T-lymphocyte cell count of 110 HIV/AIDS patients treated with traditional Chinese medicine.
Front Med
PUBLISHED: 09-03-2014
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This study aimed to evaluate the therapeutic effect of traditional Chinese medicine (TCM) by observing the changes in CD4 T-lymphocyte cell count of 110 cases with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treated continuously with TCM for 84 months. Information of 110 HIV/AIDS patients from 19 provinces and cities treated with TCM from 2004 to 2013 was collected. Changes in the indexes of CD4 counts ( ? 200, 201-350, 351-500 and > 500 cells/mm(3)) at five time points (0, 12, 36, 60 and 84 months) and different treatments [TCM and TCM plus antiretroviral therapy (ART)] were compared. Repeated measures test indicated no interaction between group and time (P > 0.05). Degrees of increasing and decreasing CD4 count of the two groups at four different frames were statistically significant compared with the baseline. The CD4 count between the two groups was not statistically significant. For CD4 count of ? 200 cells/mm(3), the mean CD4 count changes were 21 and 28 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 201-350 cells/mm(3), the mean CD4 count changes were 6 and 25 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 351-500 cells/mm(3), the mean CD4 count changes were -13 and -7 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of > 500 cells/mm(3), the mean CD4 count changes were -34 and -17 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. Long-term use of TCM could maintain or slow the pace of declining CD4 counts in patients with HIV/AIDS, and may achieve lasting effectiveness.
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miR181c promotes apoptosis and suppresses proliferation of metanephric mesenchyme cells by targeting Six2 in vitro.
Cell Biochem. Funct.
PUBLISHED: 09-03-2014
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Increasingly recognized importance has been assumed for microRNA (miRNA) in the regulation of the delicate balance of gene expression. In our study, we aimed to explore the regulation role of miR181c towards Six2 in metanephric mesenchyme (MM) cells. Bioinformatics analysis, luciferase assay and semi-quantitative real-time (RT) PCR, subsequently RT PCR, Western blotting, 5-ethynyl-2'-deoxyuridine cell proliferation assay, Cell Counting Kit-8 assay, immunofluorescence and flow cytometry, were employed to verify the modulation function of miR181c on Six2 in the mK3 MM cell line that is one kind of MM cells. miR181c was predicted to bind the 3' untranslated region of Six2 by bioinformatics analysis, which was subsequently validated by the in vitro luciferase reporter assay. Moreover, transfection of miR181c mimic can decrease the expression of Six2 both in mRNA and protein levels in mK3 cells. Still, ectopic expression of miR181c inhibits the proliferation, promotes the apoptosis and even makes the nephron progenitor phenotype lose mK3 cells. These results revealed the ability of a single miRNA-miR181c to downregulate the expression of Six2, restrain the proliferation and promote the apoptosis that even makes the nephron progenitor phenotype lose MM cells, suggesting a potential role of miR181c during the kidney development. Copyright © 2014 John Wiley & Sons, Ltd.
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[Association between APOC3 promoter region polymorphisms and non-alcoholic fatty liver disease].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-03-2014
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To investigate the association between two polymorphisms of the APOC3 gene (T-455C and C-482T) and hereditary risk of non-alcoholic fatty liver disease (NAFLD).
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Intraoperative anthropometric measurements of tibial morphology: comparisons with the dimensions of current tibial implants.
Knee Surg Sports Traumatol Arthrosc
PUBLISHED: 09-02-2014
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This study analyzed morphological differences in the resected proximal tibial surfaces of Chinese males and females undergoing total knee arthroplasty (TKA) and compared the measurements with the dimensions of five currently used tibial implants.
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Hemorrhagic Transformation after Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke: Mechanisms, Models, and Biomarkers.
Mol. Neurobiol.
PUBLISHED: 09-01-2014
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Intracerebral hemorrhagic transformation (HT) is well recognized as a common cause of hemorrhage in patients with ischemic stroke. HT after acute ischemic stroke contributes to early mortality and adversely affects functional recovery. The risk of HT is especially high when patients receive thrombolytic reperfusion therapy with tissue plasminogen activator, the only available treatment for ischemic stroke. Although many important publications address preclinical models of ischemic stroke, there are no current recommendations regarding the conduct of research aimed at understanding the mechanisms and prediction of HT. In this review, we discuss the underlying mechanisms for HT after ischemic stroke, provide an overview of the models commonly used for the study of HT, and discuss biomarkers that might be used for the early detection of this challenging clinical problem.
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Genome sequence and genetic diversity of the common carp, Cyprinus carpio.
Nat. Genet.
PUBLISHED: 08-29-2014
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The common carp, Cyprinus carpio, is one of the most important cyprinid species and globally accounts for 10% of freshwater aquaculture production. Here we present a draft genome of domesticated C. carpio (strain Songpu), whose current assembly contains 52,610 protein-coding genes and approximately 92.3% coverage of its paleotetraploidized genome (2n = 100). The latest round of whole-genome duplication has been estimated to have occurred approximately 8.2 million years ago. Genome resequencing of 33 representative individuals from worldwide populations demonstrates a single origin for C. carpio in 2 subspecies (C. carpio Haematopterus and C. carpio carpio). Integrative genomic and transcriptomic analyses were used to identify loci potentially associated with traits including scaling patterns and skin color. In combination with the high-resolution genetic map, the draft genome paves the way for better molecular studies and improved genome-assisted breeding of C. carpio and other closely related species.
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The Advantages of Unilateral Pedal Lymphography in the Diagnosis of Chyluria.
Urol. Int.
PUBLISHED: 08-22-2014
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Objectives: To evaluate the efficacy and safety of pedal lymphography (PLG) in the localization diagnosis of chyluria. Methods: Cystoscopy was performed in 153 patients and PLG in 121 cases. Unilateral or staged bilateral ligation and stripping of renal lymphatic vessel were performed according to the results of cystoscopy and/or PLG. Results: Unilateral and bilateral urinary excretion of chyle was detected in 123 and 1 case by cystoscopy, respectively. In 121 cases receiving PLG, 100 cases of unilateral fistulous connection between the renal pelvis and the lymphatic system, 18 cases of bilateral fistulas and 1 case of lymphatic bladder fistula were demonstrated. PLG has a higher diagnostic rate for the detection of bilateral lymphatic renal pelvis fistulas than cystoscopy (p < 0.05). 28 cases received renal pedicle lymphatic disconnection only according to the results of cystoscopy, and 3 of them failed (10.1%). While 121 cases had the same operation according to the results of PLG, only 1 case failed the operation (0.8%). Conclusions: PLG was efficient and safe for the localization diagnosis of chyluria, with a higher detection rate of bilateral fistulas than cystoscopy. PLG might benefit the selection of appropriate therapy and improve the surgical effect. © 2014 S. Karger AG, Basel.
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Morphologic changes in the anterior and posterior subregions of V1 and V2 and the V5/MT+ in patients with primary open-angle glaucoma.
Brain Res.
PUBLISHED: 08-20-2014
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The aim of this study was to investigate possible morphologic changes of the visual cortex in primary open-angle glaucoma (POAG) with varying severity. Twenty normal controls (NC), 19 mild (MP) and 17 severe (SP) POAG patients were recruited and scanned using magnetic resonance imaging. Multi-parameter morphologic analyses with regions of interest (V5/MT+, anterior and posterior subregions of V1 and V2) were used to assess the cortical changes among the three groups. Compared with the NC group, decreased cortical thickness was detected in the V5/MT+ area in the MP group and in all of the investigated visual areas except the posterior subregion of V1 in the SP group. Unexpectedly, cortical thinning of the posterior subregion of V2 was detected in the SP group compared with the NC and MP groups. For the other morphologic parameters, only gray matter volume in the posterior subregion of V2 and mean curvature in the V5/MT+ were significantly changed in the SP group. In addition, the clinical measurements were positively correlated with the cortical thickness of the V5/MT+ and the posterior subregion of V2. In conclusion, the V5/MT+ area is involved in early disruption of POAG and the cortical degeneration may be progressive and heterogeneous in different visual cortices. Early neuroprotective therapies on the retina and central visual system may help to preserve vision in patients with POAG.
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Hexane Cracking over Steamed Phosphated Zeolite H-ZSM-5: Promotional Effect on Catalyst Performance and Stability.
Chemistry
PUBLISHED: 08-19-2014
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The nature behind the promotional effect of phosphorus on the catalytic performance and hydrothermal stability of zeolite H-ZSM-5 has been studied using a combination of (27) Al and (31) P MAS NMR spectroscopy, soft X-ray absorption tomography and n-hexane catalytic cracking, complemented with NH3 temperature-programmed desorption and N2 physisorption. Phosphated H-ZSM-5 retains more acid sites and catalytic cracking activity after steam treatment than its non-phosphated counterpart, while the selectivity towards propylene is improved. It was established that the stabilization effect is twofold. First, the local framework silico-aluminophosphate (SAPO) interfaces, which form after phosphatation, are not affected by steam and hold aluminum atoms fixed in the zeolite lattice, preserving the pore structure of zeolite H-ZSM-5. Second, the four-coordinate framework aluminum can be forced into a reversible sixfold coordination by phosphate. These species remain stationary in the framework under hydrothermal conditions as well. Removal of physically coordinated phosphate after steam-treatment leads to an increase in the number of strong acid sites and increased catalytic activity. We propose that the improved selectivity towards propylene during catalytic cracking can be attributed to local SAPO interfaces located at channel intersections, where they act as impediments in the formation of bulky carbenium ions and therefore suppress the bimolecular cracking mechanism.
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Lewis Base Catalyzed Aerobic Oxidative Intermolecular Azide-Zwitterion Cycloaddition.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-15-2014
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The discovery of a novel aerobic oxidative intermolecular azide-zwitterion reaction catalyzed by an organocatalyst is presented. It is demonstrated that the merger of the Lewis base 1,8-diazabicyclo[5.4.0]undec-7-ene and electron-deficient olefins generates reactive zwitterion intermediates, which readily participate in cycloaddition reactions with an array of azides, thus providing facile entry to fully or highly substituted 1,2,3-triazole frameworks. The reaction features an excellent substrate scope, and the products are obtained with high yields and excellent regioselectivities. It is demonstrated that some of these products can be transformed into pharmaceutically important agents. In addition to the experimental results, a detailed mechanistic survey is also provided, including MS studies rationalizing the origin of regioselective control.
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Long-range hybrid wedge plasmonic waveguide.
Sci Rep
PUBLISHED: 08-13-2014
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We design a novel long-range hybrid wedge plasmonic (LRHWP) waveguide composed of two identical dielectric nanowires symmetrically placed on two opposed wedges of a diamond shaped metal wire. With strong coupling between the dielectric nanowire mode and long-range surface plasmon polariton (SPP) mode, both deep subwavelength mode confinement and low propagation loss are achieved. On one hand, when compared to the previous long-range hybrid SPP waveguide, LRHWP waveguide can achieve smaller mode size with similar propagation length; on the other hand, when compared to the previous hybrid wedge SPP waveguide, LRHWP waveguide can provide an order of magnitude longer propagation length with similar level of mode confinement. The designed LRHWP waveguide also features an overall advantage of one-order improvement of Figure of Merit. We further evaluate in detail the impacts of possible practical fabrication imperfections on the mode properties. The obtained results of mode properties show that the proposed LRHWP waveguide with an optimized wedge tip angle of 140 degree is fairly tolerant to practical fabrication errors in geometry parameters such as misalignment in the horizontal direction, asymmetry in the vertical direction, variation of wedge tip angle, tilt or rotation of metal wire, and variation of wedge tip curvature radius.
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Assessing technical performance in differential gene expression experiments with external spike-in RNA control ratio mixtures.
Nat Commun
PUBLISHED: 08-11-2014
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There is a critical need for standard approaches to assess, report and compare the technical performance of genome-scale differential gene expression experiments. Here we assess technical performance with a proposed standard 'dashboard' of metrics derived from analysis of external spike-in RNA control ratio mixtures. These control ratio mixtures with defined abundance ratios enable assessment of diagnostic performance of differentially expressed transcript lists, limit of detection of ratio (LODR) estimates and expression ratio variability and measurement bias. The performance metrics suite is applicable to analysis of a typical experiment, and here we also apply these metrics to evaluate technical performance among laboratories. An interlaboratory study using identical samples shared among 12 laboratories with three different measurement processes demonstrates generally consistent diagnostic power across 11 laboratories. Ratio measurement variability and bias are also comparable among laboratories for the same measurement process. We observe different biases for measurement processes using different mRNA-enrichment protocols.
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Deficiency of female sex hormones augments PGE2 and CGRP levels within midbrain periaqueductal gray.
J. Neurol. Sci.
PUBLISHED: 08-10-2014
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The midbrain periaqueductal gray (PAG) is a substantial component of the descending modulatory network to control on nociceptive transmission and autonomic functions. Also, accumulated evidence has suggested that the PAG plays a crucial role in regulating migraine headache, a neurovascular disorder. The purpose of this study was to employ ELISA methods to examine the levels of prostaglandin E2 (PGE2) and calcitonin-gene related peptide (CGRP) in the PAG of rats who received ovariectomy and subsequent hormone replacement with 17?-estradiol, progesterone, or the combination of 17?-estradiol and progesterone. In addition, using Western blot analysis we examined expression of subtypes of PGE2 receptor in the PAG of rats with different conditions of female sex hormones. Results of our study demonstrated that lack of female sex hormones significantly increased the levels of PGE2 and CGRP in the dorsolateral PAG (P<0.05) as well as expression of PGE2 EP3 receptors (P<0.05). Furthermore, a liner relationship was observed between PGE2 and CGRP in the PAG (r=092, P<0.01). Also, inhibiting EP3 receptors by chronic administration of L-798106 (EP3 antagonist) into the lateral ventricles significantly attenuated expression of CGRP in the PAG of ovariectomized animals (P<0.05 vs. vehicle control). Overall, our findings for the first time show that (1) circulating 17?-estradiol and/or progesterone influences the levels of PGE2 and CGRP in the PAG; (2) a lower level of 17?-estradiol and/or progesterone augments PGE2 and its EP3 receptor; and (3) PGE2 plays a role in regulating expression of CGRP in the PAG.
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TNFR1 mediates TNF-?-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling.
Nat Commun
PUBLISHED: 08-07-2014
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Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-? markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-?-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism. However, VEGFR3-induced lymphatic endothelial cell tips are a prerequisite for lymphatic vessel growth in vivo, and a VEGFR3 blockade completely ablates TNF-?-induced lymphangiogenesis. Moreover, TNF-?-TNFR1-activated inflammatory macrophages produce high levels of VEGF-C to coordinately activate VEGFR3. Genetic deletion of TNFR1 (Tnfr1(-/-)) in mice or depletion of tumour-associated macrophages (TAMs) virtually eliminates TNF-?-induced lymphangiogenesis and lymphatic metastasis. Gain-of-function experiments show that reconstitution of Tnfr1(+/+) macrophages in Tnfr1(-/-) mice largely restores tumour lymphangiogenesis and lymphatic metastasis. These findings shed mechanistic light on the intimate interplay between inflammation and lymphangiogenesis in cancer metastasis, and propose therapeutic intervention of lymphatic metastasis by targeting the TNF-?-TNFR1 pathway.
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Magnetic Resonance Imaging with Gadoxetic Acid Disodium for the Detection of Hepatocellular Carcinoma: A Meta-analysis of 18 Studies.
Acad Radiol
PUBLISHED: 08-06-2014
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To determine the accuracy of magnetic resonance imaging (MRI) with gadoxetic acid disodium for the detection of hepatocellular carcinoma (HCC).
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Antenna Allocation in MIMO Radar with Widely Separated Antennas for Multi-Target Detection.
Sensors (Basel)
PUBLISHED: 07-22-2014
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In this paper, we explore a new resource called multi-target diversity to optimize the performance of multiple input multiple output (MIMO) radar with widely separated antennas for detecting multiple targets. In particular, we allocate antennas of the MIMO radar to probe different targets simultaneously in a flexible manner based on the performance metric of relative entropy. Two antenna allocation schemes are proposed. In the first scheme, each antenna is allocated to illuminate a proper target over the entire illumination time, so that the detection performance of each target is guaranteed. The problem is formulated as a minimum makespan scheduling problem in the combinatorial optimization framework. Antenna allocation is implemented through a branch-and-bound algorithm and an enhanced factor 2 algorithm. In the second scheme, called antenna-time allocation, each antenna is allocated to illuminate different targets with different illumination time. Both antenna allocation and time allocation are optimized based on illumination probabilities. Over a large range of transmitted power, target fluctuations and target numbers, both of the proposed antenna allocation schemes outperform the scheme without antenna allocation. Moreover, the antenna-time allocation scheme achieves a more robust detection performance than branch-and-bound algorithm and the enhanced factor 2 algorithm when the target number changes.
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MiR-133b Contributes to Arsenic-Induced Apoptosis in U251 Glioma Cells by Targeting the hERG Channel.
J. Mol. Neurosci.
PUBLISHED: 07-10-2014
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Substantial evidence indicates that the human ether-a-go-go-related gene potassium channel (hERG, Kv11.1, KCNH2) is overexpressed in human glioblastoma multiforme (GBM) specimens and plays an essential role in the malignant proliferation of glioma cells. However, its upstream regulator in glioma cells is not fully elucidated. The present study was designed to determine whether the expression of hERG gene is regulated by miR-133b or miR-34a, thereby contributing to the anti-proliferation effect of arsenic trioxide (ATO) in U251 human glioma cells. Real-time polymerase chain reactions (qRT-PCR) and Western blot results demonstrated that hERG mRNA and protein levels were dramatically upregulated in clinical GBM specimens. Conversely, both miR-133b and miR-34a were markedly downregulated in clinical GBM specimens by qRT-PCR. The hERG gene was a direct target of miR-133b and miR-34a by bioinformatics analyses and luciferase reporter assays. Moreover, ATO, which is an emerging chemotherapy drug for glioma disease, remarkably elevated the level of miR-133b, but not miR-34a in U251 glioma cells. The level of miR-133b upstream transactivator serum response factor (SRF) was also suppressed by ATO. The transfection of anti-miR-133b oligonucleotide (AMO-133b) remarkably prevented the decrease of hERG protein by 5 ?M ATO treatment for 24 h in U251 cells, whereas anti-miR-34a oligonucleotide (AMO-34a) did not exhibit recuperated effect. Finally, the transient overexpression by miR-133b mimics and treatment with the hERG channel-specific blocker E4031 markedly facilitated the ATO inhibition of proliferation of and induced apoptosis in U251 cells, whereas AMO-miR-133b attenuated these changes. Our study provided the evidence for the pathological role of miR-133b and miR-34a in the development of GBM and thus expanded our understanding of the hERG gene expression and ATO chemotherapeutic roles of miRNAs. Targeting miR-133b/hERG pathway may be a new strategy for chemotherapy of malignant gliomas.
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The Roles of Neurotensin and its Analogues in Pain.
Curr. Pharm. Des.
PUBLISHED: 07-09-2014
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Neurotensin (NT) is an endogenous 13 amino acid neuropeptide with profound opioid-independent analgesic effects. This role of NT is thought to be mediated by both neurotensin receptor subtype 1 (NTS1) and neurotensin receptor subtype 2 (NTS2). NT and its receptors are widely distributed in the pain circuits in central nervous system. Thus NT might modulate pain in many structures of pain pathway, such as spinal cord, rostroventral medulla (RVM) and periaqueductal gray (PAG). Actually either intrathecal application of NT or direct injection of NT into RVM or PAG or intracerebroventricular injection of NT showed analgesic effects. NT exerted its antinociceptive effects in both acute pain and chronic pain models. The analgesic effects of NT were originally found in acute pain experiments. In the case of pathological pain, for example, formalin injection induced inflammatory pain and sciatic nerve constriction induced neuropathic pain, NT also shows antinociceptive effects. The effects exist in somatic pain as well as visceral pain induced by noxious colorectal distension (CRD) or writhing test. It should be noted that NT plays an important role in stress-induced antinociception (SIAN), especially in higher intensity stress experiments. However as a neuropeptide, NT is susceptible to degradation by peptidases and cannot cross the blood-brain barrier (BBB). Great efforts have been made to find NT analogues that are more biologically stable and could inhibit pain by systematic administration. The present review focuses on the analgesic role and the underlying mechanisms of NT and its analogues in pain, especially in chronic pain models.
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Peroxisome proliferator-activated receptor ? inhibits pulmonary hypertension targeting store-operated calcium entry.
J. Mol. Med.
PUBLISHED: 07-07-2014
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In this study, we investigated the role of peroxisome proliferator-activated receptor ? (PPAR?) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPAR? agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1?, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPAR? exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1? accumulation. We also found that under hypoxia, accumulated Hif-1? protein acts as upstream of suppressed PPAR? level; however, targeted PPAR? rescue acts as negative feedback on suppressing Hif-1? level and Hif-1? mediated signaling pathway. PPAR? inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1? expression and signaling transduction.
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Osseointegration of chitosan coated porous titanium alloy implant by reactive oxygen species-mediated activation of the PI3K/AKT pathway under diabetic conditions.
Biomaterials
PUBLISHED: 07-03-2014
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Chitosan coated porous titanium alloy implant (CTI) is demonstrated a promising approach to improve osseointegration capacity of pure porous titanium alloy implant (TI). Since chitosan has been demonstrated to exhibit antioxidant activity, we propose CTI may ameliorate the ROS overproduction, thus reverse the poor osseointegration under diabetic conditions, and investigate the underlying mechanisms. Primary rat osteoblasts incubated on the TI and the CTI were subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and DS + LY294002 (a PI3K/AKT-specific inhibitor). In vivo study was performed on diabetic sheep implanted with TI or CTI into the bone defects on crista iliaca. Results showed that diabetes-induced ROS overproduction led to osteoblast dysfunction and apoptosis, concomitant with the inhibition of AKT in osteoblasts on the TI substrate. While CTI stimulated AKT phosphorylation through ROS attenuation, thus reversed osteoblast dysfunction evidenced by improved osteoblast adhesion, increased proliferation and ALP activity, and decreased cytotoxicity and apoptotic rate, which exerted same effect to NAC treatment on the TI. These effects were further confirmed by the improved osseointegration within the CTI in vivo evidenced by Micro-CT and histological examinations. In addition, the aforementioned promotive effects afforded by CTI were abolished by blocking PI3K/AKT pathway with addition of LY294002. These results demonstrate that the chitosan coating markedly ameliorates diabetes-induced impaired bio-performance of TI via ROS-mediated reactivation of PI3K/AKT pathway, which elicits a new surface functionalization strategy for better clinical performance of titanium implant in diabetic patients.
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EphA3, induced by PC-1/PrLZ, contributes to the malignant progression of prostate cancer.
Oncol. Rep.
PUBLISHED: 06-27-2014
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Our previous study revealed the potential linkage of PC-1/PrLZ, a novel isolated prostate-specific gene, to the progression of prostate cancer (PCa) in vitro and in vivo. To gain more insight into the mechanism of PC-1-induced promotion of PCa, expression analysis of differential genes induced by PC-1 was scanned by microarray. Among all the differentially expressed genes, EphA3 was altered to the greatest extent. EphA3 has been identified to be associated with multiple tumor progression. However, little is known concerning the function of EphA3 in PCa. In the present study, we aimed to ascertain whether EphA3 is induced by PC-1 and the functional significance of EphA3 expression in PCa. We found that overexpression of PC-1 increased the amount of EphA3 and that knockdown of PC-1 led to a decrease in EphA3 in PCa cells. The functional significance and mechanisms by which EphA3 contributes to PCa was investigated in vitro using cell lines, and in vivo using a mouse model and clinical specimens. The results showed that EphA3 enhanced the proliferation and survival of LNCaP cells and suppression of EphA3 inhibited the survival of C4-2B cells. EphA3 enhanced the tumor development of LNCaP cells in null mice. A positive correlation between the levels of EphA3 and the Gleason grade of PCa was identified in clinical PCa specimens. In addition, cellular localization changed with Gleason grade. We further detected that EphA3 increased phosphorylation of Akt (Ser473 and Thr308), indicating that EphA3 activated the Akt pathway. Taken together, EphA3 was induced by PC-1 and contributed to the malignant progression of prostate cancer. Our results provide the first demonstration that EphA3 is a novel promoter of human prostate cancer development and progression.
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Extrarenal nephroblastomatosis in children: a report of two cases.
BMC Pediatr
PUBLISHED: 06-24-2014
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Extrarenal nephroblastomatosis is a rare entity which occurs in retroperitoneum and inguinal region predominantly. Here we report two cases of primary extrarenal nephroblastomatosis of Han Chinese in Asian in unusual locations, one is located in testis and paratestis, and the other is paraspinal cord.
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Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients.
Int. J. Mol. Med.
PUBLISHED: 06-21-2014
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Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of human cancer. However, ZNF382 expression and methylation status in pediatric AML is unknown. In the present study, ZNF382 transcription levels were evaluated by quantitative reverse-transcription PCR. Methylation status was investigated by methylation-specific (MSP) PCR and bisulfate genomic sequencing (BGS). The prognostic significance of ZNF382 expression and promoter methylation was assessed in 105 cases of pediatric AML. The array data suggested that the ZNF382 promoter was hypermethylated in the AML cases examined. MSP PCR and BGS analysis revealed that ZNF382 was hypermethylated in leukemia cell lines. Furthermore, treatment with 5-aza-2'-deoxycytidine (5-Aza) upregulated ZNF382 expression in the selected leukemia cell lines. The aberrant methylation of ZNF382 was observed in 10% (2/20) of the control samples compared with 26.7% (28/105) of the AML samples. ZNF382 expression was significantly decreased in the 105 AML patients compared with the controls. Patients with ZNF382 methylation showed lower ZNF382 transcript levels compared with patients exhibiting no methylation. There were no significant differences in clinical characteristics or cytogenetic analysis between the patients with or without ZNF382 methylation. ZNF382 methylation correlated with minimal residual disease (MRD). Kaplan-Meier survival analysis revealed similar survival times in the samples with ZNF382 methylation, and multivariate analysis revealed that ZNF382 methylation was not an independent prognostic factor in pediatric AML. The epigenetic inactivation of ZNF382 by promoter hypermethylation can be observed in AML cell lines and pediatric AML samples. Therefore, our study suggests that ZNF382 may be considered a putative tumor suppressor gene in pediatric AML. However, further studies focusing on the mechanisms responsible for ZNF382 downregulation in pediatric leukemia are required.
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Analysis of metabolic characteristics in a rat model of chronic pancreatitis using high?resolution magic?angle spinning nuclear magnetic resonance spectroscopy.
Mol Med Rep
PUBLISHED: 06-18-2014
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Pathological and metabolic alterations co?exist and co?develop in the progression of chronic pancreatitis (CP). The aim of the present study was to investigate the metabolic characteristics and disease severity of a rat model of CP in order to determine associations in the observed pathology and the metabolites of CP using high?resolution magic?angle spinning nuclear magnetic resonance spectroscopy (HR?MAS NMR). Wistar rats (n=36) were randomly assigned into 6 groups (n=6 per group). CP was established by administering dibutyltin dichloride solution into the tail vein. After 0, 7, 14, 21, 28 and 35 days, the pancreatic tissues were collected for pathological scoring or for HR?MAS NMR. Correlation analyses between the major pathological scores and the integral areas of the major metabolites were determined. The most representative metabolites, aspartate, betaine and fatty acids, were identified as possessing the greatest discriminatory significance. The Spearman's rank correlation coefficients between the pathology and metabolites of the pancreatic tissues were as follows: Betaine and fibrosis, 0.454 (P=0.044); betaine and inflammatory cell infiltration, 0.716 (P=0.0001); aspartate and fibrosis, ?0.768 (P=0.0001); aspartate and inflammatory cell infiltration, ?0.394 (P=0.085); fatty acid and fibrosis, ?0.764 (P=0.0001); and fatty acid and inflammatory cell infiltration, ?0.619 (P=0.004). The metabolite betaine positively correlated with fibrosis and inflammatory cell infiltration in CP. In addition, aspartate negatively correlated with fibrosis, but exhibited no significant correlation with inflammatory cell infiltration. Furthermore, the presence of fatty acids negatively correlated with fibrosis and inflammatory cell infiltration in CP. HR?MAS NMR may be used to analyze metabolic characteristics in a rat model of different degrees of chronic pancreatitis.
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A co-culture model with brain tumor-specific bioluminescence demonstrates astrocytes-induced drug resistance in glioblastoma.
J Transl Med
PUBLISHED: 06-12-2014
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BackgroundAlthough several studies suggest that stromal fibroblasts mediate treatment resistance in several cancer types, little is known about how tumor-associated astrocytes modulate the treatment response in brain tumors. Since traditionally used metabolic assays do not distinguish metabolic activity between stromal and tumor cells as well as 2-dimensional co-culture system does not recreate the formidable complexity of the microenvironment within 3-dimensional structures such as solid tumor tissue, we instead established a glioblastoma (GBM) cell-specific bioluminescent assay for direct measurements of tumor cell viability in the treatment of clinical relevant drugs.MethodsUsing lentiviral transfection, we established a panel of human GBM cell lines constitutively expressing a fusion transgene encoding luciferase and the enhanced green fluorescence protein (eGFP). We then initiated co-cultures with immortalized astrocytes, TNC-1, and the eGFP/Luc GBM cell lines. We then treated all eGFP/Luc GBM cell lines with Temozolomide (TMZ) and Doxorubicin, comparing co-cultures of glioblastoma (GBM) cells and TNC-1 astrocytes with mono-cultures of eGFP/Luc GBM cells. Cell viability was quantitated by measuring the luciferase expression.ResultsTitration experiments demonstrated that luciferase expression was proportional to the number of eGFP/Luc GBM cells, whereas it was not influenced by the number of TNC-1 cells present. Notably, the presence of TNC-1 astrocytes mediated significantly higher cell survival after TMZ treatment in the U251, C6, A172 cell lines as well as the in vivo propagated primary GBM tumor cell line (P3). Moreover, TNC-1 astrocytes mediated significantly higher survival after Doxorubicin treatment in the U251, and LN18 glioma cell lines.ConclusionGlioma cell-specific bioluminescent assay is a reliable tool for assessment of cell viability in the brain tumor cell compartment following drug treatment. Moreover, we have applied this assay to demonstrate that astrocytes can modulate chemo sensitivity of GBM tumor cells. These effects varied both with the cell line and cytotoxic drug that were used, suggesting that several mechanisms may be involved.
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Cancer survival in China, 2003-2005: A population-based study.
Int. J. Cancer
PUBLISHED: 06-09-2014
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Limited population-based cancer registry data available in China until now has hampered efforts to inform cancer control policy. Following extensive efforts to improve the systematic cancer surveillance in this country, we report on the largest pooled analysis of cancer survival data in China to date. Of 21 population-based cancer registries, data from 17 registries (n?=?138,852 cancer records) were included in the final analysis. Cases were diagnosed in 2003-2005 and followed until the end of 2010. Age-standardized relative survival was calculated using region-specific life tables for all cancers combined and 26 individual cancers. Estimates were further stratified by sex and geographical area. The age-standardized 5-year relative survival for all cancers was 30.9% (95% confidence intervals: 30.6%-31.2%). Female breast cancer had high survival (73.0%) followed by cancers of the colorectum (47.2%), stomach (27.4%), esophagus (20.9%), with lung and liver cancer having poor survival (16.1% and 10.1%), respectively. Survival for women was generally higher than for men. Survival for rural patients was about half that of their urban counterparts for all cancers combined (21.8% vs. 39.5%); the pattern was similar for individual major cancers except esophageal cancer. The poor population survival rates in China emphasize the urgent need for government policy changes and investment to improve health services. While the causes for the striking urban-rural disparities observed are not fully understood, increasing access of health service in rural areas and providing basic health-care to the disadvantaged populations will be essential for reducing this disparity in the future.
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