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Find video protocols related to scientific articles indexed in Pubmed.
Sonic hedgehog signalling pathway regulates apoptosis through Smo protein in human umbilical vein endothelial cells.
Rheumatology (Oxford)
PUBLISHED: 11-20-2014
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The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells.
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TCRklass: A New K-String-Based Algorithm for Human and Mouse TCR Repertoire Characterization.
J. Immunol.
PUBLISHED: 11-19-2014
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The next-generation sequencing technology has promoted the study on human TCR repertoire, which is essential for the adaptive immunity. To decipher the complexity of TCR repertoire, we developed an integrated pipeline, TCRklass, using K-string-based algorithm that has significantly improved the accuracy and performance over existing tools. We tested TCRklass using manually curated short read datasets in comparison with in silico datasets; it showed higher precision and recall rates on CDR3 identification. We applied TCRklass on large datasets of two human and three mouse TCR repertoires; it demonstrated higher reliability on CDR3 identification and much less biased V/J profiling, which are the two components contributing the diversity of the repertoire. Because of the sequencing cost, short paired-end reads generated by next-generation sequencing technology are and will remain the main source of data, and we believe that the TCRklass is a useful and reliable toolkit for TCR repertoire analysis.
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Catalytic asymmetric Povarov reaction of isatin-derived 2-azadienes with 3-vinylindoles.
Org. Biomol. Chem.
PUBLISHED: 10-20-2014
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The first catalytic asymmetric Povarov reaction of isatin-derived 2-azadienes with 3-vinylindoles was established in the presence of chiral phosphoric acid, which tolerates a wide range of substrates with generally excellent diastereoselectivity and good enantioselectivity (up to >95?:?5 dr, 89?:?11 er). This approach will greatly enrich the chemistry of the catalytic asymmetric Povarov reaction, in particular ketone-involved transformations. Furthermore, this protocol represents the first diastereo- and enantio-selective construction of a spiro[indolin-3,2'-quinoline] framework bearing an indole moiety. This novel type of spiro-compound not only contains two chiral centers, including one quaternary stereogenic center, but also integrates two biologically important structures of spiro[indolin-3,2'-quinoline] and indole, which may find medicinal applications after bioassay.
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[Determination of chemical rank of three-dimensional fluorescence spectra using mathematical morphology method].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 10-02-2014
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The present paper firstly denoises the signal with morphological method, selecting sine-shaped structure element, using the morphological difference in waveform between the three-dimensional fluorescence and noise signal, then singular value decomposition is applied to the denoised data, and finally the chemical rank is determinated jointing eigenvalues and eigenvectors form singular value decomposition. This paper principally discusses the theory basis of morphological filtering method, firstly simulated data is analysed by morphological filtering method to confirm the necessity and effectiveness of proposed method, then the feasibility and practicability of the proposed method is verified by the determination of components number of phenols mixture three-dimensional fluorescence spectra compared with traditional Monte Carlo method. The experiments demonstrate that the proposed method is able to estimate the chemical rank correctly.
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[Analysis of heavy metals distribution characteristics and pollution assessment in agricultural region soils of Huaihe basin].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 10-02-2014
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By means of field sampling and laboratory analysis, the content distribution characteristics of Cd, Cr, Cu, Ni, Pb and Zn in agricultural region soils of Huaihe basin in Anhui province were analyzed. Assessment of heavy metal pollutions was conducted using enrichment factor, geoaccumulation index and potential ecological risk index. The results showed that the average mass fraction of Cd and Cu was 0.113 5 and 22.09 mg x kg(-1) respectively in the study area soil, which were above the background values 0.097 and 20.4 mg x kg(-1) in Anhui Province. The average mass fraction of other four heavy metals did not exceed the average values of Anhui Province. The results of the evaluations from geoaccumulation index and ecological risk assessment discovered that Cd is the strongest pollution metal among six heavy metals in the study area soil. For some samples of the study soil, Cd was slight risk for the ecosystem. The ecosystem risks caused by the other five heavy metals were not obviously for the sampling points. The entire study area soils were mid integrated potential ecological risk.
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Systematic dissection of the mechanisms underlying progesterone receptor downregulation in endometrial cancer.
Oncotarget
PUBLISHED: 09-18-2014
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Progesterone, acting through its receptor, PR (progesterone receptor), is the natural inhibitor of uterine endometrial carcinogenesis by inducing differentiation. PR is downregulated in more advanced cases of endometrial cancer, thereby limiting the effectiveness of hormonal therapy. Our objective was to understand and reverse the mechanisms underlying loss of PR expression in order to improve therapeutic outcomes. Using endometrial cancer cell lines and data from The Cancer Genome Atlas, our findings demonstrate that PR expression is downregulated at four distinct levels. In well-differentiated cancers, ligand-induced receptor activation and downregulation are intact. miRNAs mediate fine tuning of PR levels. As differentiation is lost, PR silencing is primarily at the epigenetic level. Initially, recruitment of the polycomb repressor complex 2 to the PR promoter suppresses transcription. Subsequently, DNA methylation prevents PR expression. Appropriate epigenetic modulators reverse these mechanisms. These data provide a rationale for combining epigenetic modulators with progestins as a therapeutic strategy for endometrial cancer.
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Synergistic increase of oxidative stress and tumor markers in PAH-exposed workers.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-18-2014
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In this study, we investigated oxidative stress and tumor marker levels of polycyclic aromatic hydrocarbons (PAHs) in 136 coke oven workers and in 60 control subjects, and evaluated the correlation between oxidative stress and tumor marker levels. Questionnaires on basic demographic information were also administered. Significant differences in employment time and percentages of alcohol drinkers were observed between the control and exposed groups. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. Significant differences (P<0.001) of MDA, GST, LDH, NSE, Cyfra21-1, and of SCC and TNF-a (P<0.0001 and P<0.05, P<0.001, respectively) levels were observed among controls and coke-oven workers, except for bottom coke oven workers. Associations between age and risk of increased TNF-a, smoking and increased GST activities, and drinking with increased MDA concentrations, were marginal (P=0.055, P=0.048, P=0.057, respectively). The association between smoking with MDA (P=0.004), NSE (P=0.005), SCC (P=0.004) and TNF-a (P<0.001), and drinking with TNF-a levels was significant (P=0.012). In addition, a significant positive correlation between oxidative stress and tumor markers was found in the present study. These results suggest that a synergistic increase of oxidative stress and tumor markers induced by PAHs may play a role in toxic responses for PAHs in coke oven workers.
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[Analysis of three-dimensional fluorescence overlapping spectra using nonnegative matrix factorization].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 09-12-2014
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The present paper primarily tests and verifies the effect of NMF in blind source separation of three-dimensional simulative fluorescence spectra, and then four different computational algorithms (multiplicative iterative; alternating least square; second order method; projected gradient algorithm) were used in three practical phenolic compounds (cresol, phenol, thymol) overlapping fluorescence spectra to find out which nonnegatively constrained algorithms is the most efficient for fluorescence spectra unmixing. The experiments demonstrate that four ways have the normalized residuals below 0.06%, and alternating least square (ALS) is the best at both convergence behavior and robustness.
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Rh(I)-catalyzed decarbonylative direct C2-olefination of indoles with vinyl carboxylic acids.
Chem. Commun. (Camb.)
PUBLISHED: 09-05-2014
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A general and efficient Rh(I)-catalyzed decarbonylative direct C2-olefination of indoles with vinyl carboxylic acids has been developed. The reaction exhibits excellent functional group tolerance, regioselectivity and stereoselectivity, giving a broad range of C2-alkenylated indoles in good to excellent yields.
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Angiotensin II Activates Signal Transducers and Activators of Transcription 3 via Rac1 in the Atrial Tissue in Permanent Atrial Fibrillation Patients with Rheumatic Heart Disease.
Cell Biochem. Biophys.
PUBLISHED: 08-24-2014
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Patients with rheumatic heart disease (RHD) often experience persistent atrial fibrillation (AF) associated with adverse atrial structural remodeling (ASR) manifested by atrial fibrosis and left atrial enlargement. The aim of this study was to explore the potential molecular signaling mechanisms for atrial fibrosis and ASR. Twenty RHD patients with persistent AF and 10 RHD patients with sinus rhythm (Group A) were recruited in our study, which all underwent transthoracic echocardiography. Right atrial appendage (RAA) tissue samples were obtained from these patients during mitral/aortic valve replacement operation. The AF patients were further divided into two groups according to left atrial diameter (LAD): Group B with LAD ranging 50-65 mm and Group C with LAD >65 mm. Histological examinations were performed with hematoxylin-eosin staining and Masson's trichrome staining. Atrial angiotensin II (AngII) content was measured by ELISA. Rac1 and STAT3 protein levels were determined by Western blot analysis. Hematoxylin-eosin staining demonstrated highly organized arrangement of atrial muscles in control Group A and significant derangement in both Group B and C AF patients with reduced cell density and increased cell size. Moreover, Masson's trichrome staining showed that atrial myocytes were surrounded by large trunks of collagen fibers in both Group B and C, but not in Group A. There was a positive correlation between atrial tissue fibrosis and LAD. AngII content was markedly higher in Group C than in Group B than in Group A, which was positively correlated with LAD. Similarly, Rac1 and STAT3 protein levels were found considerably higher in Group C and B than in Group A with excellent correlation to LAD. Our study unraveled for the first time the AngII/Rac1/STAT3 signaling as a mechanism for ASR thereby AF in a particular clinical setting-RHD patients with persistent AF and indicated inhibition of this pathway may help ameliorating adverse ASR.
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SIX1 promotes tumor lymphangiogenesis by coordinating TGF? signals that increase expression of VEGF-C.
Cancer Res.
PUBLISHED: 08-20-2014
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Lymphatic vessels are one of the major routes for the dissemination of cancer cells. Malignant tumors release growth factors such as VEGF-C to induce lymphangiogenesis, thereby promoting lymph node metastasis. Here, we report that sine oculis homeobox homolog 1 (SIX1), expressed in tumor cells, can promote tumor lymphangiogenesis and lymph node metastasis by coordinating with TGF? to increase the expression of VEGF-C. Lymphangiogenesis and lymph node metastasis in cervical cancer were closely correlated with higher expression of SIX1 in tumor cells. By enhancing VEGF-C expression in tumor cells, SIX1 could augment the promoting effect of tumor cells on the migration and tube formation of lymphatic endothelial cells (LEC) in vitro and lymphangiogenesis in vivo. SIX1 enhanced TGF?-induced activation of SMAD2/3 and coordinated with the SMAD pathway to modulate VEGF-C expression. Together, SIX1 and TGF? induced much higher expression of VEGF-C in tumor cells than each of them alone. Despite its effect in promoting VEGF-C expression, TGF? could inhibit lymphangiogenesis by directly inhibiting tube formation by LECs. However, the increased production of VEGF-C not only directly promoted migration and tube formation of LECs but also thwarted the inhibitory effect of TGF? on LECs. That is, tumor cells that expressed high levels of SIX1 could promote lymphangiogenesis and counteract the negative effects of TGF? on lymphangiogenesis by increasing the expression of VEGF-C. These findings provide new insights into tumor lymphangiogenesis and the various roles of TGF? signaling in tumor regulation. Our results also suggest that SIX1/TGF? might be a potential therapeutic target for preventing lymph node metastasis of tumor.
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Volatilization of arsenic from polluted soil by Pseudomonas putida engineered for expression of the arsM Arsenic(III) S-adenosine methyltransferase gene.
Environ. Sci. Technol.
PUBLISHED: 08-14-2014
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Even though arsenic is one of the most widespread environmental carcinogens, methods of remediation are still limited. In this report we demonstrate that a strain of Pseudomonas putida KT2440 endowed with chromosomal expression of the arsM gene encoding the As(III) S-adenosylmethionine (SAM) methyltransfase from Rhodopseudomonas palustris to remove arsenic from contaminated soil. We genetically engineered the P. putida KT2440 with stable expression of an arsM-gfp fusion gene (GE P. putida), which was inserted into the bacterial chromosome. GE P. putida showed high arsenic methylation and volatilization activity. When exposed to 25 ?M arsenite or arsenate overnight, most inorganic arsenic was methylated to the less toxic methylated arsenicals methylarsenate (MAs(V)), dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAs(V)O). Of total added arsenic, the species were about 62 ± 2.2% DMAs(V), 25 ± 1.4% MAs(V) and 10 ± 1.2% TMAs(V)O. Volatilized arsenicals were trapped, and the predominant species were dimethylarsine (Me2AsH) (21 ± 1.0%) and trimethylarsine (TMAs(III)) (10 ± 1.2%). At later times, more DMAs(V) and volatile species were produced. Volatilization of Me2AsH and TMAs(III) from contaminated soil is thus possible with this genetically engineered bacterium and could be instrumental as an agent for reducing the inorganic arsenic content of soil and agricultural products.
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A novel anti-proliferative role of HMGA2 in induction of apoptosis through Caspase-2 in primary human fibroblast cells.
Biosci. Rep.
PUBLISHED: 07-24-2014
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The HMGA2 protein has previously been shown as an oncoprotein, whereas ectopic expression of HMGA2 is found to induce growth arrest in primary cells. The precise mechanisms underlying this phenomenon remain to be unraveled. In this study, we determined that HMGA2 was able to induce apoptosis in WI38 primary human cells. We show that WI38 cells expressing high level of HMGA2 were arrested at G2/M phase and exhibited apoptotic nuclear phenotypes. Meanwhile, the cleaved Caspase-3 was detected 8 days after HMGA2 overexpression. Flow cytometric analysis confirmed that the ratio of cells undergoing apoptosis increased dramatically. Concurrently, other major apoptotic markers were also detected, including the upregulation of p53, Bax and cleaved Caspase-9, downregulation of Bcl-2; as well as release of Cytochrome C from the mitochondria. We further demonstrate that the shRNA-mediated Apaf1 silencing partially rescued the HMGA2-induced apoptosis, which was accompanied by the decrease of cleaved Caspase-3 level and a decline of cell death ratio.Our results also reveal that ?H2A was accumulated in nuclei during the HMGA2-induced apoptosis along with the upregulation of cleaved Caspase-2, suggesting that the HMGA2-induced apoptosis was dependent on the pathway of DNA damage. Furthermore, we found that the Wnt pathway was inhibited after HMGA2 overexpression, with a concurrent downregulation of the IAP factor survivin. Overall, this study unraveled a novel function of HMGA2 in induction of apoptosis in human primary cell lines, and provided clues for clarification of the mechanistic action of HMGA2 in addition to its function as an oncoprotein.
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Synthesis, antibacterial activities, and theoretical studies of dicoumarols.
Org. Biomol. Chem.
PUBLISHED: 06-21-2014
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Four dicoumarols (DC, 2-PyDC, 3-PyDC and 4-PyDC) were synthesized and characterized via IR, (1)H NMR, HRMS, and single crystal X-ray crystallography. Two classical intramolecular O-H···O hydrogen bonds (HBs) stabilized their structures. The total HB energies in DC, 2-PyDC, 3-PyDC and 4-PyDC were calculated with the density functional theory (DFT) [B3LYP/6-31G*] method. The in vitro antibacterial activity of DC, 2-PyDC, 3-PyDC and 4-PyDC against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), and USA 300 (Los Angeles County clone, LAC) was evaluated by observing the minimum inhibitory concentration and time-kill curves. The results showed that among all the compounds, 2-PyDC exhibited the most potent antibacterial activity.
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[Study on a new method of fast monitoring toxicity of Cd2+ by algal in water].
Huan Jing Ke Xue
PUBLISHED: 06-21-2014
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Chlorophyll concentration and photosynthesis activity fluorescence parameters of Chlorella pyrenoidosa stressed by different concentrations of Cd2+ were measured based on algal growth inhibition tests and photosynthetic activity inhibition tests. The relationship between the algal photosynthetic activity inhibition rate and 96 h inhibition rate of specific growth rate at different Cd2+ stress times was studied by sigmoidal curve fitting and one-way ANOVA analysis. The result shows that S function relevance exists between the algal photosynthetic activity inhibition rates for 48 h, 53 h, 72 h, 77 h and 96 h respectively and 96 h inhibition rate of specific growth rate (R2 > 0.95). Consequently, EC10 (10% effective concentration) after 48 h and 53 h inhibition in photosynthetic activity inhibition tests could be used to represented EC50 (50% effective concentration) in 96 h algal growth inhibition tests for evaluating the Cd2+ toxicity. Dose-response relationships between the algal photosynthetic activity inhibition rates after 48 h and 53 h inhibition and Cd2+ toxic equivalency quantity were further analyzed. The method provided a rapid and viable new thought to monitoring single Cd2+ toxicity in lab and early warn integrated toxicity of pollution in water.
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Rare Streptomyces sp. polyketides as modulators of K-Ras localisation.
Org. Biomol. Chem.
PUBLISHED: 05-31-2014
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Chemical investigations of a soil-derived Streptomyces sp. led to the isolation of five new polyketides, (+)-oxanthromicin, (±)-hemi-oxanthromicins A/B, (±)-spiro-oxanthromicin A and oxanthroquinone, and the known alkaloid staurosporine, and the detection of four new metastable analogues, (±)-spiro-oxanthromicins B1/B2/C1/C2. Among the compounds tested, SAR investigations established that the synthetic oxanthroquinone ethyl ester and 3-O-methyl-oxanthroquinone ethyl ester were optimal at mislocalising oncogenic mutant K-Ras from the plasma membrane of intact Madin-Darby canine kidney (MDCK) cells (IC50 4.6 and 1.2 ?M), while a sub-EC50 dose of (±)-spiro-oxanthromicin A was optimal at potentiating (750%) the K-Ras inhibitory activity of staurosporine (IC50 60 pM). These studies demonstrate that a rare class of Streptomyces polyketide modulates K-Ras plasma membrane localisation, with implications for the future treatment of K-Ras dependent cancers.
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Lamellarin O, a pyrrole alkaloid from an Australian marine sponge, Ianthella sp., reverses BCRP mediated drug resistance in cancer cells.
Mar Drugs
PUBLISHED: 05-29-2014
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ATP binding cassette (ABC) transporters, such as P-gp, BCRP and MRP1, can increase efflux of clinical chemotherapeutic agents and lead to multi-drug resistance (MDR) in cancer cells. While the discovery and development of clinically useful inhibitors has proved elusive to date, this molecular target nevertheless remains a promising strategy for addressing and potentially overcoming MDR. In a search for new classes of inhibitor, we used fluorescent accumulation and efflux assays supported by cell flow cytometry and MDR reversal assays, against a panel of sensitive and MDR human cancer cell lines, to evaluate the marine sponge co-metabolites 1-12 as inhibitors of P-gp, BCRP or MRP1 initiated MDR. These studies identified and characterized lamellarin O (11) as a selective inhibitor of BCRP mediated drug efflux. A structure-activity relationship analysis inclusive of the natural products 1-12 and the synthetic analogues 13-19, supported by in silico docking studies, revealed key structural requirements for the lamellarin O (11) BCRP inhibitory pharmacophore.
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Intrinsically de-sialylated CD103(+) CD8 T cells mediate beneficial anti-glioma immune responses.
Cancer Immunol. Immunother.
PUBLISHED: 05-16-2014
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Cancer vaccines reproducibly cure laboratory animals and reveal encouraging trends in brain tumor (glioma) patients. Identifying parameters governing beneficial vaccine-induced responses may lead to the improvement of glioma immunotherapies. CD103(+) CD8 T cells dominate post-vaccine responses in human glioma patients for unknown reasons, but may be related to recent thymic emigrant (RTE) status. Importantly, CD8 RTE metrics correlated with beneficial immune responses in vaccinated glioma patients.
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Inhibition of human natural killer cell functional activity by human aspartyl ?-hydroxylase.
Int. Immunopharmacol.
PUBLISHED: 05-08-2014
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Natural killer (NK) cells are a key component of the innate immune system and play pivotal roles as inflammatory regulators and in tumor surveillance. Human aspartyl ?-hydroxylase (HAAH) is a plasma membrane and endoplasmic reticulum protein with hydroxylation activity, which is over-expressed in many malignant neoplasms and can be detected from the sera of tumor patients. HAAH is involved in regulating tumor cell infiltration and metastasis. Escaping from immune surveillance may help tumor cell infiltration and metastasis. However, the effects of HAAH on tumor immune surveillance have not yet been investigated carefully. The present study investigated the potential use of HAAH as an immune regulator of human NK cells. We assessed the effects of recombinant HAAH (r-HAAH) on primary human NK cell morphology, viability, cytotoxicity, apoptosis, receptors expression and cytokine/cytolytic proteins production. Our results demonstrated that r-HAAH negatively affects NK cell activity in a time and dose-dependent manner. It noticeably reduces the viability of the NK cells by increasing apoptosis and necrosis via caspase signaling pathways. Moreover, r-HAAH reduces the NK cell cytotoxicity by inhibiting surface expression of NKG2D, NKp44 and IFN-? secretion. These findings suggest that one of the ways by which HAAH actively promotes tumor formation and proliferation is by inhibiting NK cell-surveillance activity.
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C3 glomerulopathy: the genetic and clinical findings in dense deposit disease and C3 glomerulonephritis.
Semin. Thromb. Hemost.
PUBLISHED: 05-05-2014
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C3 glomerulopathy (C3G) defines a group of very rare renal diseases in which dysregulation of the alternative and terminal complement pathways plays a pivotal pathogenic role. Dysregulation is driven by genetic and/or acquired defects, with interindividual variability giving rise to two broad subtypes of C3G-dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). Patient evaluation should include genetic testing and biomarker profiling of complement activity. There is currently no effective targeted treatment option for C3G and, as a consequence, a variety of supportive measures are used. C3G remains an ideal disease in which new complement therapies can be tested as they become available. Trials must include a comprehensive evaluation of each patient at the genetic and biomarker level so that individual responses to therapy can be predicted and understood in light of the degree of complement dysregulation and underlying pathology.
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[Research on night visibility estimation method based on image features of dual light sources].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 05-03-2014
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Haze, rain and snow bring a lot of inconvenience in our daily life, especially produce serious potential safety hazard for night transport. In the present paper the authors propose the vision-based dual light sources visibility method to estimate night visibility. This method is significantly advantaged with wide range, high precision and low cost, and has a good robustness in many kinds of weather conditions. Firstly, the authors give the basic visibility estimation model under the atmosphere multiple scattering theory. Secondly, the authors propose the dual light sources method to remove the luminance fluctuations of light sources and the atmosphere light effect, and formulize the algorithm to accurately gain information of light sources from the dual light sources image. At last, the authors design the dual light sources system and conduct a long time experiments under various atmosphere conditions. The experiments show that, with the baseline of 35 m, the visibility range is up to 15 000 m, and relative error is below 20%. This method and system can satisfy the demand of meteorological department and transport agency.
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Enhancement of dynein-mediated autophagosome trafficking and autophagy maturation by ROS in mouse coronary arterial myocytes.
J. Cell. Mol. Med.
PUBLISHED: 04-15-2014
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Dynein-mediated autophagosome (AP) trafficking was recently demonstrated to contribute to the formation of autophagolysosomes (APLs) and autophagic flux process in coronary arterial myocytes (CAMs). However, it remains unknown how the function of dynein as a motor protein for AP trafficking is regulated under physiological and pathological conditions. The present study tested whether the dynein-mediated autophagy maturation is regulated by a redox signalling associated with lysosomal Ca(2+) release machinery. In primary cultures of CAMs, reactive oxygen species (ROS) including H2 O2 and O2 (-.) (generated by xanthine/xanthine oxidase) significantly increased dynein ATPase activity and AP movement, which were accompanied by increased lysosomal fusion with AP and APL formation. Inhibition of dynein activity by (erythro-9-(2-hydroxy-3-nonyl)adenine) (EHNA) or disruption of the dynein complex by dynamitin (DCTN2) overexpression blocked ROS-induced dynein activation, AP movement and APL formation, and resulted in an accumulation of AP along with a failed breakdown of AP. Antagonism of nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca(2+) signalling with NED-19 and PPADS abolished ROS-enhanced lysosomal Ca(2+) release and dynein activation in CAMs. In parallel, all these changes were also enhanced by overexpression of NADPH oxidase-1 (Nox1) gene in CAMs. Incubation with high glucose led to a marked O2 (-.) production compared with normoglycaemic CAMs, while Nox1 inhibitor ML117 abrogated this effect. Moreover, ML117 and NED-19 and PPADS significantly suppressed dynein activity and APL formation caused by high glucose. Taken together, these data suggest that ROS function as important players to regulate dynein-dependent AP trafficking leading to efficient autophagic maturation in CAMs.
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Triptolide inhibits cell proliferation and tumorigenicity of human neuroblastoma cells.
Mol Med Rep
PUBLISHED: 04-10-2014
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Triptolide is a diterpene triepoxide, extracted from the Chinese herb Tripterygium wilfordii Hook F, which has been shown to have antitumor activity in a number of cancers. Neuroblastoma is an aggressive extracranial pediatric solid tumor, with significant chemotherapeutic resistance. In this study, triptolide was hypothesized to be a potential therapeutic agent for neuroblastoma. The effects of triptolide on neuroblastoma cell growth and tumor development were investigated. Cell growth and proliferation were evaluated using a cell counting kit?8 assay and a 5-bromo-2-deoxyuridine staining assay. Cell cycle and apoptosis were detected by flow cytometry. Reverse transcription?quantitative polymerase chain reaction was conducted to detect the expression levels of the apoptosis?associated proteins, caspase?3 and caspase?9. The tumorigenicity of neuroblastoma cells was assessed by a soft agar clonogenic assay and an in vivo tumorigenic assay. The results demonstrated that exposure of BE(2)?C human neuroblastoma cells to triptolide resulted in a reduction in cell growth and proliferation, and the induction of cell death and apoptosis, together with cell cycle arrest in the S phase. A soft agar assay indicated that triptolide inhibited the colony?forming ability of BE(2)?C neuroblastoma cells. The xenograft experiment showed that triptolide significantly reduced tumor growth and development in vivo. The data suggested that this Chinese herb may be a potential novel chemotherapeutic agent for neuroblastoma.
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Dihydroartemisinin accentuates the anti-tumor effects of photodynamic therapy via inactivation of NF-?B in Eca109 and Ec9706 esophageal cancer cells.
Cell. Physiol. Biochem.
PUBLISHED: 04-09-2014
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Photodynamic therapy (PDT) is a new treatment for esophageal cancer which has been shown to be effective in the elimination of tumor. However, PDT could induce the activation of nuclear factor-kappa B (NF-?B) in many photosensitizers based PDT, which plays a negative role in PDT. In addition, our previous results have shown that dihydroartemisinin (DHA), which was the most potent one of artemisinin derivatives, has anticancer activity in esophageal cancer cells.
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Sonodynamically induced anti-tumor effect of 5-aminolevulinic acid on pancreatic cancer cells.
Ultrasound Med Biol
PUBLISHED: 03-19-2014
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Sonodynamic therapy (SDT), a promising modality for cancer treatment, involves the synergistic interaction of ultrasound and some chemical compounds termed sonosensitizers. However, its effect on pancreatic cancer cells remains unclear. In our study, we sought to identify the cytotoxic effects of ultrasound-activated 5-aminolevulinic acid on human pancreatic cancer Capan-1 cells. Cell viability was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) analysis; mitochondrial membrane potential was assessed using the fluorescent probe jc-1; apoptosis was evaluated by flow cytometry; cell morphology was investigated by scanning electron microscopy; apoptosis-related protein expression was analyzed by Western blot assay. We found that SDT significantly decreased the survival rate of cells, and this effect increased with 5-aminolevulinic acid concentration and ultrasound exposure time. The mechanism underlying the effect of SDT involves, in part, the induction of a conspicuous loss in mitochondrial membrane potential and, in part, the induction of apoptosis through upregulation of Bax expression, downregulation of Bcl-2 and increased activation of procaspase-3. These results indicate that the ultrasonically induced cell killing effect could be enhanced by 5-ALA and that the mitochondrial pathway might be involved in the cell damage process. We conclude that SDT is a promising new methodology for pancreatic cancer treatment.
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Sine oculis homeobox homolog 1 promotes DNA replication and cell proliferation in cervical cancer.
Int. J. Oncol.
PUBLISHED: 03-19-2014
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Malignant proliferation is the fundamental trait of tumor cells. The initiation of DNA replication represents a key process for cell proliferation, and has a marked impact on tumorigenesis and progression. Here we report that Sine oculis homeobox homolog 1 (SIX1) functions as a master regulator in DNA replication of cervical cancer cells. The expression of SIX1 was induced by the E7 oncoprotein of human papillomaviruses in cervical intraepithelial neoplasia and cervical cancer. The increase of SIX1 expression resulted in the upregulation of multiple genes related to the initiation of DNA replication, including the genes coding for the proteins in minichromosome maintenance complex (MCM2, MCM3, MCM6), DNA polymerase ?-primase complex (POLA1, PRIM1, PRIM2), clamp loader (RFC3, RFC4, RFC5), DNA polymerase ? complex (POLD3) and DNA polymerase ? complex (POLE2). In line with this, the increase of SIX1 expression enhanced DNA synthesis, accelerated G1 to S phase progression, and promoted the proliferation of cervical cancer cells and the growth of cervical cancer. Consistently, knockdown of SIX1 could hamper DNA synthesis, slow down G1 to S phase progression, and suppress tumor cell proliferation and tumor growth. Importantly, SIX1 could more efficiently promote anchorage-independent cell growth. These results suggest that the increase of SIX1 expression could promote tumorigenesis, progression and invasive growth of cervical cancer by promoting DNA replication, and that targeting SIX1 may have significant therapeutic value in cervical cancer treatment.
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Characterization of human ??TCR repertoire and discovery of D-D fusion in TCR? chains.
Protein Cell
PUBLISHED: 03-01-2014
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The characterization of the human T-cell receptor (TCR) repertoire has made remarkable progress, with most of the work focusing on the TCR? chains. Here, we analyzed the diversity and complexity of both the TCR? and TCR? repertoires of three healthy donors. We found that the diversity of the TCR? repertoire is higher than that of the TCR? repertoire, whereas the usages of the V and J genes tended to be preferential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly preferential. We also found that the TRDV1 gene rearranges with the majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene (TRAV42/DV1). Moreover, we uncovered the presence of tandem TRBD (TRB D gene) usage in ~2% of the productive human TCR? CDR3 sequences.
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Sine oculis homeobox homolog 1 promotes ?5?1-mediated invasive migration and metastasis of cervical cancer cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 02-25-2014
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Sine oculis homeobox homolog 1 (SIX1) has been supposed to be correlated with the metastasis and poor prognosis of several malignancies. However, the effect of SIX1 on the metastatic phenotype of tumor cells and the underlying mechanisms were still unclear to date. Here we report that SIX1 can promote ?5?1-mediated metastatic capability of cervical cancer cells. SIX1 promoted the expression of ?5?1 integrin to enhance the adhesion capacity of tumor cells in vitro and tumor cell arrest in circulation in vivo. Moreover, higher expression of SIX1 in tumor cells resulted in the increased production of active MMP-2 and MMP-9, up-regulation of anti-apoptotic genes (BCL-XL and BCL2) and down-regulation of pro-apoptotic genes (BIM and BAX), thus promoting the invasive migration and anoikis-resistance of tumor cells. Importantly, blocking ?5?1 abrogated the regulatory effect of SIX1 on the expression of these genes, and also abolished the promotional effect of SIX1 on invasive capability of tumor cells. Furthermore, knock-down of ?5 could abolish the promoting effect of SIX1 on the development of metastatic lesions in both experimental and spontaneous metastasis model. Therefore, by up-regulating ?5?1 expression, SIX1 not only promoted the adhesion capacity, but also augmented ECM-?5?1-mediated regulation of gene expression to enhance the metastatic potential of cervical cancer cells. These results suggest that SIX1/?5?1 might be considered as valuable marker for metastatic potential of cervical cancer cells, or a therapeutic target in cervical cancer treatment.
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Essential role of GATA3 in regulation of differentiation and cell proliferation in SK-N-SH neuroblastoma cells.
Mol Med Rep
PUBLISHED: 02-22-2014
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Neuroblastoma is a common solid malignant tumor of the sympathetic nervous system, which contributes to 15% of cancer?related mortality in children. The differentiation status of neuroblastoma is correlated with clinical outcome, and the induction of differentiation thus constitutes a therapeutic approach in this disease. However, the molecular mechanisms that control the differentiation of neuroblastoma remain poorly understood. The present study aimed to define whether GATA3 is involved in the differentiation of neuroblastoma cells. The results demonstrated that GATA3 is a prognostic marker for survival in patients with neuroblastoma, and that high?level GATA3 expression is associated with increased self?renewal and proliferation of neuroblastoma cells. Retinoic acid treatment led to GATA3 downregulation together with neuronal differentiation, suppression of cell proliferation and inhibition of tumorigenecity in neuroblastoma cells. These findings suggest that GATA3 is a key regulator of neuroblastoma differentiation, and provide a novel potential therapeutic strategy for the induction of neuroblastoma differentiation.
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Therapeutic effects of PADRE-BAFF autovaccine on rat adjuvant arthritis.
Biomed Res Int
PUBLISHED: 02-17-2014
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B cell activating factor (BAFF) is a cytokine of tumor necrosis factor family mainly produced by monocytes and dendritic cells. BAFF can regulate the proliferation, differentiation, and survival of B lymphocytes by binding with BAFF-R on B cell membrane. Accumulating evidences showed that BAFF played crucial roles and was overexpressed in various autoimmune diseases such as systemic lupus erythematous (SLE) and rheumatoid arthritis (RA). This suggests that BAFF may be a therapeutic target for these diseases. In the present study, we developed a BAFF therapeutic vaccine by coupling a T helper cell epitope AKFVAAWTLKAA (PADRE) to the N terminus of BAFF extracellular domains (PADRE-BAFF) and expressed this fusion protein in Escherichia coli. The purified vaccine can induce high titer of neutralizing BAFF antibodies and ameliorate the syndrome of complete Freund's adjuvant (CFA) induced rheumatoid arthritis in rats. Our data indicated that the BAFF autovaccine may be a useful candidate for the treatment of some autoimmune diseases associated with high level of BAFF.
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Distribution of 37 human papillomavirus types in parotid gland tumor tissues.
Oncol Lett
PUBLISHED: 02-15-2014
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Human papillomavirus (HPV) infection has been shown to be associated with human tumorigenesis. The aim of the present study was to demonstrate the association between HPV infection and parotid gland tumors. Paraffin-embedded tissue sections from 59 cases of parotid gland tumors and 20 normal oral mucosa were subjected to DNA extraction and flow-through hybridization and gene chip technology to detect infection of 37 HPV types. The HPV-positive rate was 57.6% in parotid gland tumor paraffin-embedded tissue specimens, whereas, the normal control group was negative for HPV. The HPV-positive rate was 59.6% in parotid gland benign tumor tissues and 42.9% in parotid malignant tissues. HPV infection in parotid gland tumors was dominated by the high-risk subtypes (80.7%), which mainly consisted of HPV 16, 18 and 52 (61.4%). In addition, parotid gland tumor tissues were found to be infected by multiple or single types of HPV, but were predominantly infected by mixed HPV types. In this study, we found that the occurrence of parotid gland tumor is correlated with HPV infection.
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Cadmium treatment alters the expression of five genes at the Cda1 locus in two soybean cultivars [Glycine max (L.) Merr].
ScientificWorldJournal
PUBLISHED: 02-07-2014
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Westag 97 has larger capacity of Cd accumulation in roots which prevents Cd from translocating into stems and leaves; conversely, AC Hime has smaller capacity of Cd accumulation in roots; more Cd is transported into stems and leaves. The different capacity of Cd in roots between Westag 97 and AC Hime causes the different Cd concentration in seeds. Meanwhile, according to the different expression levels of RSTK, ISCP, and H(+)-ATPase between Westag 97 and AC Hime, RSTK may be involved in transporting Cd into stems and leaves; H(+)-ATPase may be correlated to the capacity of Cd accumulation in roots; and Cd caused some changes of fundamental life process which leaded to the different expression patterns of ISCP between Westag 97 and AC Hime.
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Integrating qualitative and quantitative characterization of traditional Chinese medicine injection by high-performance liquid chromatography with diode array detection and tandem mass spectrometry.
J Sep Sci
PUBLISHED: 02-05-2014
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The present study aims to describe and exemplify an integrated strategy of the combination of qualitative and quantitative characterization of a multicomponent mixture for the quality control of traditional Chinese medicine injections with the example of Danhong injection (DHI). The standardized chemical profile of DHI has been established based on liquid chromatography with diode array detection. High-performance liquid chromatography coupled with time-of-flight mass spectrometry and high-performance liquid chromatography with electrospray multistage tandem ion-trap mass spectrometry have been developed to identify the major constituents in DHI. The structures of 26 compounds including nucleotides, phenolic acids, and flavonoid glycosides were identified or tentatively characterized. Meanwhile, the simultaneous determination of seven marker constituents, including uridine, adenosine, danshensu, protocatechuic aldehyde, p-coumaric acid, rosmarinic acid, and salvianolic acid B, in DHI was performed by multiwavelength detection based on high-performance liquid chromatography with diode array detection. The integrated qualitative and quantitative characterization strategy provided an effective and reliable pattern for the comprehensive and systematic characterization of the complex traditional Chinese medicine system.
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Paris Saponin II suppresses the growth of human ovarian cancer xenografts via modulating VEGF-mediated angiogenesis and tumor cell migration.
Cancer Chemother. Pharmacol.
PUBLISHED: 02-01-2014
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Paris Saponin II (PSII) is an active component of Rhizoma Paridis-an essential ingredient in traditional Chinese herbal medicines. PSII can induce cytotoxic effects in cancer cells and inhibit ovarian cancer growth. Since pathological angiogenesis (henceforth, angiogenesis) is often associated with gynecological cancers, here, we investigated whether PSII renders effects on angiogenesis and examined possible molecular mechanisms underlying the effects of PSII.
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Expression, purification, and biological activity of the recombinant pramlintide precursor.
Appl. Microbiol. Biotechnol.
PUBLISHED: 01-29-2014
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Pramlintide is an artificially designed protein which has the same function as amylin in human body. This protein is extremely difficult to synthesize through prokaryotic expression method because of its two essential active sites, intrachain disulfide bond and C-terminal amide group. Since ?-amidating monooxygenase is widely distributed in human and animal, it is possible to use pramlintide precursor with an additional C-terminal glycine (PAG), which is the potential substrate of ?-amidating monooxygenase, for in vivo applications. The recombinant PAG was expressed in Escherichia coli using the small ubiquitin-related modifier (SUMO) as the molecular chaperone, and the optimal fusion expression level reached to 36.3% of the total supernatant protein. Under optimal conditions in a 10-L fermentor, the recombinant PAG was obtained with a purity of greater than 95%, and the average expression level was reached to 20 mg/L. The authenticity and the intrachain disulfide bridge of PAG were confirmed by Western blotting and matrix-assisted laser desorption/ionization coupled to time-of-flight mass spectrometry (MALDI-TOF MS) as well as N-terminal sequencing of protein. Based on an L6 myoblast cell model in vitro and an animal model of gastric emptying in vivo, the results of activity revealed that PAG showed a lower biological activity in vitro but has almost the same activity as the chemically synthesized pramlintide in vivo.
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Discrimination of three dimensional fluorescence spectra based on wavelet analysis and independent component analysis.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 01-28-2014
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Fluorescence spectroscopy is a rapid and non-destructive method for monitoring water quality. In this work, wavelet analysis, together with independent component analysis (ICA), was applied for component recognition of seriously overlapped, multi-component, three dimensional fluorescence spectra. Wavelet analysis extracts the features of the spectra and amplifies differences among phenolic homologs. ICA analysis in blind signal separation was used to separate single component before multiple linear regression (MLR). The proposed method increases the correct classification rate and enriches the spectra library. As such, it is a useful alternative to traditional techniques in component recognition.
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[Prevalence of syphilis during pregnancy and risk factors for maternal and perinatal infections: a 2009-2013 survey].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 01-28-2014
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To analyze the risk factors for maternal and perinatal syphilis infections in Guangzhou.
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Callyspongisines A-D: bromopyrrole alkaloids from an Australian marine sponge, Callyspongia sp.
Org. Biomol. Chem.
PUBLISHED: 01-25-2014
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An extract of the Great Australian Bight marine sponge Callyspongia sp. (CMB-01152) displayed inhibitory activity against the neurodegenerative disease kinase targets casein kinase 1 (CK1), cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3 (GSK3?). Chemical investigation, employing HPLC-DAD-MS single ion extraction protocols, facilitated identification of the new bromopyrrole alkaloids, callyspongisines A-D (1-4), and two known co-metabolites, hymenialdisine (5) and 2-bromoaldisine (6). Structure elucidation of 1-6 was supported by detailed spectroscopic analysis and chemical interconversion, as well as biosynthetic and synthetic considerations. Callyspongisine A (1) is only the second reported example of a natural imino-oxazoline, and the first to feature a spiro heterocyclic framework, while callyspongisines B-D (2-4) were speculated to be storage and handling artefacts of 1. The kinase inhibitory activity detected in Callyspongia sp. (CMB-01152) was attributed to 5.
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Prevalence of human papillomavirus and Epstein-Barr virus DNA in Chinese children with tonsillar and/or adenoidal hypertrophy.
J. Med. Virol.
PUBLISHED: 01-09-2014
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Tonsillar and adenoidal hypertrophy are prevalent otolaryngologic disorders in children, but their pathogenesis is largely unknown. The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNA in 146 tonsil and/or adenoid tissue specimens from 104 Chinese children with tonsillar and/or adenoidal hypertrophy were screened using flow-through hybridization gene-chip technology and real-time fluorescence-based quantitative PCR. Then, the relationships between the prevalence of the viruses and other clinical characteristics of tonsillar and/or adenoidal hypertrophy were analyzed. No patient had HPV DNA. EBV DNA was detected in 19/42 (45.2%) tonsil tissues and 72/104 (69.2%) adenoid tissue specimens (P?
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CT-guided sclerotherapy for simple renal cysts: value of ethanol concentration monitoring.
Korean J Radiol
PUBLISHED: 01-08-2014
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The aim of our study was to evaluate the differences between sclerotherapy with and without ethanol concentration monitoring for the treatment of simple renal cysts.
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Integrated optical gyroscope using active long-range surface plasmon-polariton waveguide resonator.
Sci Rep
PUBLISHED: 01-07-2014
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Optical gyroscopes with high sensitivity are important rotation sensors for inertial navigation systems. Here, we present the concept of integrated resonant optical gyroscope constructed by active long-range surface plasmon-polariton (LRSPP) waveguide resonator. In this gyroscope, LRSPP waveguide doped gain medium is pumped to compensate the propagation loss, which has lower pump noise than that of conventional optical waveguide. Peculiar properties of single-polarization of LRSPP waveguide have been found to significantly reduce the polarization error. The metal layer of LRSPP waveguide is electro-optical multiplexed for suppression of reciprocal noises. It shows a limited sensitivity of ~10(-4)?deg/h, and a maximum zero drift which is 4 orders of magnitude lower than that constructed by conventional single-mode waveguide.
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Inhibition of H3K9 methyltransferase G9a repressed cell proliferation and induced autophagy in neuroblastoma cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Histone methylation plays an important role in gene transcription and chromatin organization and is linked to the silencing of a number of critical tumor suppressor genes in tumorigenesis. G9a is a histone methyltransferase (HMTase) for histone H3 lysine 9. In this study, we investigated the role of G9a in neuroblastoma tumor growth together with the G9a inhibitor BIX01294. The exposure of neuroblastoma cells to BIX01294 resulted in the inhibition of cell growth and proliferation, and BIX01294 treatment resulted in the inhibition of the tumorigenicity of neuroblastoma cells in NOD/SCID mice. Therefore, G9a may be a potential therapeutic target in neuroblastoma. Moreover, we found several specific characteristics of autophagy after BIX01294 treatment, including the appearance of membranous vacuoles and microtubule-associated protein light chain 3 (LC3B). Similar results were observed in G9a-knockdown cells. In conclusion, our results demonstrated that G9a is a prognostic marker in neuroblastoma, and revealed a potential role of G9a in regulating the autophagy signaling pathway in neuroblastoma.
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The screening research of anti-inflammatory bioactive markers from different flowering phases of Flos Lonicerae Japonicae.
PLoS ONE
PUBLISHED: 01-01-2014
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Flos Lonicerae Japonicae (FLJ) is an important cash crop in eastern Asia, and it is an anti-inflammatory Traditional Chinese Medicine. There are large variations in the quality of the marketed FLJ products. To find marker ingredients useful for quality control, a tandem technology integrating ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF), principal component analysis (PCA), heat map analysis and hierarchical cluster analysis coupled with a NF-?B luciferase reporter gene assay were used to identify the different ingredients from the green bud, white bud, flowering stage and leaf stages, as well as to screen the anti-inflammatory activity of FLJ compositions. As flowering progressed, the anti-inflammatory effects of FLJ gradually decreased; however, chlorogenic acid, swertiamarin and sweroside should be used to evaluate the quality of FLJ products.
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The severe adverse reaction to vitamin k1 injection is anaphylactoid reaction but not anaphylaxis.
PLoS ONE
PUBLISHED: 01-01-2014
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The severe adverse reaction to vitamin K1 injection is always remarkable and is thought to result from anaphylaxis. Paradoxically, however, some patients administered vitamin K1 injection for the first time have adverse reactions. Using beagle dogs, the present study tested the hypothesis that the response to vitamin K1 is an anaphylactoid reaction. The results showed that serious anaphylaxis-like symptoms appeared in beagle dogs after the administration of vitamin K1 injection for the first time. The plasma histamine concentration increased, and blood pressure decreased sharply. After sensitization, dogs were challenged with vitamin K1 injection and displayed the same degree of symptoms as prior to sensitization. However, when the vitamin K1 injection-sensitized dogs were challenged with a vitamin K1-fat emulsion without solubilizers such asTween-80, the abnormal reactions did not occur. Furthermore, there was no significant change in the plasma immunoglobulin E concentration after vitamin K1 challenge. Following treatment with vitamin K1 injection, the release of histamine and ?-hexosaminidase by rat basophilic leukemia-2H3 cells as well as the rate of apoptosis increased. The Tween-80 group displayed results similar to those observed following vitamin K1 injection in vivo. However, the dogs in the vitamin K1-fat emulsion group did not display any abnormal behavior or significant change in plasma histamine. Additionally, degranulation and apoptosis did not occur in rat basophilic leukemia-2H3 cells. Our results indicate that the adverse reaction induced by vitamin K1 injection is an anaphylactoid reaction, not anaphylaxis. Vitamin K1 injection induces the release of inflammatory factors via a non-IgE-mediated immune pathway, for which the trigger may be the solubilizer.
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[Impact of resting heart rate on new-onset diabetes in population without hypertension].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 12-28-2013
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To investigate the impact of resting heart rate (RHR) on new-onset diabetes (NOD) in population without hypertension.
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[Genetic evolution analysis of matrix protein 2 gene of avian influenza H5N1 viruses from boundary of Yunnan province].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 10-12-2013
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To elucidate the variation in characterizations and genetic evolution of the matrix protein 2 or ion channel protein(M2) genes of avian influenza subtype H5N1 viruses in the boundary region of Yunnan province from 2008 to 2012.
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Mismatch repair deficiency in ovarian cancer - Molecular characteristics and clinical implications.
Gynecol. Oncol.
PUBLISHED: 10-07-2013
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DNA mismatch repair (MMR) deficiency is associated with increased risk of developing several types of cancer and is the most common cause of hereditary ovarian cancer after BRCA1 and BRCA2 mutations. While there has been extensive investigation of MMR deficiency in colorectal cancer, MMR in ovarian cancer is relatively under-investigated. This review summarizes the mechanism of MMR, the ways in which MMR deficiency can promote carcinogenesis in general and then assesses the available studies regarding MMR deficiency in ovarian cancers with specific emphasis on implications for disease incidence and therapy. The incidence of germline MMR gene mutations in ovarian cancer is only 2% but other mechanisms of gene inactivation mean that loss of expression of one of the seven main genes (MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2) occurs in up to 29% of cases. Both mutational and expression data suggest that MMR deficiency is more common in non-serous ovarian cancer. Some studies suggest an improved survival for patients with MMR deficiency compared to historical controls but these do not account for the preponderance of non-serous tumors. A number of in vitro studies have suggested that MMR deficiency is a cause of platinum resistance. To date this has not been categorically demonstrated in the clinic. Larger studies that account for stage of presentation and immunohistochemical subtype are required to assess the effect of MMR deficiency on survival and chemosensitivity. Investigation of MMR related synthetic lethality in colorectal cancer has identified dihydrofolate reductase, DNA polymerase ? and DNA polymerase ? and PTEN-induced putative kinase 1 as synthetic lethal to certain MMR defects by causing accumulation of oxidative DNA damage. These synthetic lethal targets require tested and others should be sought within the context of MMR deficient ovarian cancer in an attempt to provide novel therapeutic strategies for these patients.
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Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 09-30-2013
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Cytochrome b5 reductase 2 (CYB5R2), a member of the flavoprotein pyridine nucleotide cytochrome reductase family, is associated with a number of physiological reactions. However, its role in cancer, especially nasopharyngeal carcinoma (NPC), has not been addressed. Here, we investigate the transcript levels and promoter methylation status of CYB5R2 in NPC derived cell lines and tumor biopsies and experimentally address its role as a tumor suppressor gene. We find that CYB5R2 transcript levels are decreased in NPC cell lines and tumor biopsies. Promoter hypermethylation of CYB5R2 was detected in all six tested NPC cell lines and in 84 % of primary NPC tumor biopsies but not in normal nasopharyngeal epithelium. Clinically, CYB5R2 methylation was associated with lymph node metastasis in NPC patients (P?
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[Genetic evolution of non-structural gene among avian influenza H5N1 viruses isolated from the boundary of Yunnan province].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 09-11-2013
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To elucidate the characteristics of variation and the genetic evolution of non-structural protein (NS1, NS2) genes related to avian influenza subtype H5N1 viruses isolated from the boundary region of Yunnan province.
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HLA-A, HLA-B, HLA-DRB1 polymorphisms and risk of cervical squamous epithelial cell carcinoma: a population study in China.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-03-2013
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Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphisms have been shown to associate with cervical cancer risk, but results varied among different populations. In this study, the HLA-A, -B, and -DRB1 alleles among 100 southern Chinese women with cervical squamous cell carcinoma (SCC) were compared to 254 controls. Our results showed that B*51:01:02 allele frequency was significantly higher in patients with SCC than that in healthy controls (P = 3.17x 10-5, Pc = 0.005, OR = 26.68). Statistical analysis also revealed a significantly decreased frequency of B*51:01:01 (P = 7.01x 10-4, Pc = 0.03, OR = 0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-B*51:01:02 may confer susceptibility to SCC and HLA-B*51:01:01 may contribute to the resistance to the development of SCC in Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in cases and controls after multiple testing corrections, implicating those individual allele associations are independent of the identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved with susceptibility for developing SCC.
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Integrated Laplacian-based phase unwrapping and background phase removal for quantitative susceptibility mapping.
NMR Biomed
PUBLISHED: 08-29-2013
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Quantitative susceptibility mapping (QSM) is a recently developed MRI technique that provides a quantitative measure of tissue magnetic susceptibility. To compute tissue magnetic susceptibilities based on gradient echoes, QSM requires reliable unwrapping of the measured phase images and removal of contributions caused by background susceptibilities. Typically, the two steps are performed separately. Here, we present a method that simultaneously performs phase unwrapping and HARmonic (background) PhasE REmovaL using the LAplacian operator (HARPERELLA). Both numerical simulations and in vivo human brain images show that HARPERELLA effectively removes both phase wraps and background phase, whilst preserving all low spatial frequency components originating from brain tissues. When compared with other QSM phase preprocessing techniques, such as path-based phase unwrapping followed by background phase removal, HARPERELLA preserves the tissue phase signal in gray matter, white matter and cerebrospinal fluid with excellent robustness, providing a convenient and accurate solution for QSM. The proposed algorithm is provided, together with QSM and susceptibility tensor imaging (STI) tools, in a shared software package named STI Suite. Copyright © 2013 John Wiley & Sons, Ltd.
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Regulation of autophagic flux by dynein-mediated autophagosomes trafficking in mouse coronary arterial myocytes.
Biochim. Biophys. Acta
PUBLISHED: 07-11-2013
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Autophagic flux is an important process during autophagy maturation in coronary arterial myocytes (CAMs). Here, we defined the role and molecular mechanism of the motor protein dynein in the regulation of autophagic flux in CAMs. In mouse CAMs, dynein protein is abundantly expressed. Pharmacological or genetic inhibition of dynein activity dramatically enhanced 7-ketocholesterol (7-Ket)-induced expression of the autophagic marker LC3B and increased the cellular levels of p62, a selective substrate for autophagy. Inhibition of dynein activity increased 7-Ket-induced formation of autophagosomes (APs), but reduced the number of autophagolysosomes (APLs) in CAMs. Furthermore, 7-Ket increased the fusion of APs with lysosomes and the velocity of APs movement in mouse CAMs, which was abolished when the dynein activity in these cells was inhibited. Interestingly, 7-Ket increased lysosomal Ca(2+) release and stimulated dynein ATPase activity, both of which were abolished by NAADP antagonists, NED-19 and PPADS. Taken together, our data suggest that NAADP-mediated Ca(2+) release plays a crucial role in regulating dynein activity, which mediates APs trafficking and fusion with lysosomes to form APLs thus regulating autophagic flux in CAMs under atherogenic stimulation.
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Effectiveness of CT-guided sclerotherapy with estimated ethanol concentration for treatment of symptomatic simple hepatic cysts.
Clin Res Hepatol Gastroenterol
PUBLISHED: 07-03-2013
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The mean Hounsfield value of 99.9% ethanol did get down to -190 Hounsfield units (HU), there was a linear correlation between ethanol concentration and Hounsfield values. We aimed to evaluate whether sclerotherapy with estimated ethanol concentration was helpful in improving the success rate for treatment of symptomatic simple hepatic cysts.
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A novel hybrid CFHR1/CFH gene causes atypical hemolytic uremic syndrome.
Pediatr. Nephrol.
PUBLISHED: 06-21-2013
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Mutations in complement factor H (CFH) are associated with complement dysregulation and the development of an aggressive form of atypical hemolytic uremic syndrome (aHUS) that progresses to end-stage renal disease (ESRD) and in most patients has a high rate of recurrence following transplantation. Sequence analysis of CFH and its downstream complement factor H-related genes (CFHR1-5) reveals several macrohomologous blocks caused by large genomic duplications. This high degree of sequence identity renders this area susceptible to nonallelic homologous recombination (NAHR) events, resulting in large-scale deletions, duplications, and the generation of hybrid CFH genes.
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Sesterterpene glycinyl-lactams: a new class of glycine receptor modulator from Australian marine sponges of the genus Psammocinia.
Org. Biomol. Chem.
PUBLISHED: 06-11-2013
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Bioassay guided fractionation of three southern Australian marine sponges of the genus Psammocinia, selected for their ability to modulate glycine-gated chloride channel receptors (GlyRs), yielded the rare marine sesterterpenes (-)-ircinianin (1) and (-)-ircinianin sulfate (2), along with the new biosynthetically related metabolites (-)-ircinianin lactam A (3), (-)-ircinianin lactam A sulfate (4), (-)-oxoircinianin (5), (-)-oxoircinianin lactam A (6) and (-)-ircinianin lactone A (7). Acetylation of 1 returned (-)-ircinianin acetate (8). Whole cell patch-clamp electrophysiology on 1-8 established 3 as an exceptionally potent and selective ?3 GlyR potentiator, and 6 as a selective ?1 GlyR potentiator. The discovery and characterization of sesterterpenes 1-8, and in particular the glycinyl-lactams 3 and 6, provide valuable new insights into GlyR pharmacology. These insights have the potential to inform and inspire the development of new molecular tools to probe GlyR distribution and function, and therapeutics to treat a wide array of GlyR mediated diseases and disorders.
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[Drug resistance of methicillin resistant Staphylococcus strains in burn ward and relative analysis].
Zhonghua Shao Shang Za Zhi
PUBLISHED: 05-29-2013
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To study the distribution and drug resistance of methicillin resistant Staphylococcus strains in various specimens of inpatients in burn wards, and to provide reference for clinical treatment.
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Synthesis, crystal structures, and anti-drug-resistant Staphylococcus aureus activities of novel 4-hydroxycoumarin derivatives.
Eur. J. Pharmacol.
PUBLISHED: 05-13-2013
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Four novel 4-hydroxycoumarin derivatives (4-MBH, 3-MBH, 4-MDT and 3-MDT) were successfully synthesized and their structures were verified by single-crystal X-ray crystallography. All target compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), and USA 300 (Los Angeles County clone, LAC). The minimum inhibitory concentration and time-kill curves were obtained for the test compounds and antibiotics. Among the tested compounds, 3-MBH showed the most potent antibacterial activities.
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Dysbiosis signature of fecal microbiota in colorectal cancer patients.
Microb. Ecol.
PUBLISHED: 05-03-2013
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The human gut microbiota is a complex system that is essential to the health of the host. Increasing evidence suggests that the gut microbiota may play an important role in the pathogenesis of colorectal cancer (CRC). In this study, we used pyrosequencing of the 16S rRNA gene V3 region to characterize the fecal microbiota of 19 patients with CRC and 20 healthy control subjects. The results revealed striking differences in fecal microbial population patterns between these two groups. Partial least-squares discriminant analysis showed that 17 phylotypes closely related to Bacteroides were enriched in the gut microbiota of CRC patients, whereas nine operational taxonomic units, represented by the butyrate-producing genera Faecalibacterium and Roseburia, were significantly less abundant. A positive correlation was observed between the abundance of Bacteroides species and CRC disease status (R = 0.462, P = 0.046 < 0.5). In addition, 16 genera were significantly more abundant in CRC samples than in controls, including potentially pathogenic Fusobacterium and Campylobacter species at genus level. The dysbiosis of fecal microbiota, characterized by the enrichment of potential pathogens and the decrease in butyrate-producing members, may therefore represent a specific microbial signature of CRC. A greater understanding of the dynamics of the fecal microbiota may assist in the development of novel fecal microbiome-related diagnostic tools for CRC.
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CDH5 is specifically activated in glioblastoma stemlike cells and contributes to vasculogenic mimicry induced by hypoxia.
Neuro-oncology
PUBLISHED: 05-03-2013
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A proportion of glioblastoma stemlike cells (GSCs) expressing endothelial cell marker CDH5 (vascular-endothelial-cadherin or CD144) can transdifferentiate into endothelial cells and form blood vessels. However, the implications of CDH5 expression in gliomas and how it is regulated in GSCs remain to be clarified.
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Cytochrome P450 2A13 is an efficient enzyme in metabolic activation of aflatoxin G1 in human bronchial epithelial cells.
Arch. Toxicol.
PUBLISHED: 04-23-2013
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Cytochrome P450 2A13 (CYP2A13) is an extrahepatic enzyme that mainly expresses in human respiratory system, and it is reported to mediate the metabolic activation of aflatoxin B1. Due to the structural similarity, AFG1 is predicted to be metabolized by CYP2A13. However, the role of CYP2A13 in metabolic activation of AFG1 is unclear. In present study, human bronchial epithelial cells that stably express CYP2A13 (B-2A13) were used to conduct the effects of AFG1 on cytotoxicity, apoptosis, DNA damages, and their response protein expression. Low concentrations of AFG1 induced significant cytotoxicity and apoptosis, which was consistent with the increased expressions of pro-apoptotic proteins, such as C-PARP and C-caspase-3. In addition, AFG1 increased 8-OHdG and ?H2AX in the nuclies and induced S phase arrest and DNA damage in B-2A13 cells, and the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and ?H2AX, were activated. All the above effects were inhibited by nicotine (a substrate of CYP2A13) or 8-MOP (an inhibitor of CYP enzymes), confirming that CYP2A13 mediated the AFG1-induced cytotoxicity and DNA damages. Collectively, our findings first demonstrate that CYP2A13 might be an efficient enzyme in metabolic activation of AFG1 and helps provide a new insight into adverse effects of AFG1 in human respiratory system.
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Soluble Tie2 fusion protein decreases peritoneal angiogenesis in uremic rats.
Mol Med Rep
PUBLISHED: 04-23-2013
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Angiogenesis is considered to be one of the most common mechanisms leading to ultrafiltration failure (UFF) in long-term peritoneal dialysis (PD) patients. The angiopoietin (Ang)/Tie system was found to play a role in the initiation of pathological neoangiogenesis and is also involved in peritoneal angiogenesis caused by peritoneal fluid. This aim of this study was to investigate the effects of the soluble Tie2 fusion protein (sTie2/Fc) on peritoneal angiogenesis in PD-treated uremic rats. The rats were divided into 6 groups: normal, sham surgery, uremic rats without PD, uremic PD-treated rats, uremic rats treated with PD and sTie2/Fc (0.25 µg/100 g) and uremic rats treated with PD and sTie2/Fc (0.5 µg/100 g). PD rats were treated once a day for 28 days prior to testing. Real-time polymerase chain reaction (RT-PCR) or tissue immunohistochemical staining was used to detect Ang-2 mRNA or protein expression in the peritoneal tissues of each group. The microvessel density (MVD) of the peritoneum was detected and quantified by immunohistochemical staining using the anti-CD34 antibody. Compared with the control group, Ang-2 mRNA and protein expression was significantly upregulated in the uremic and PD groups (P<0.05). MVD in the experimental group increased compared with the control group. sTie2/Fc treatment decreased the levels of Ang-2 mRNA and protein expression (P<0.05) in a dose-dependent manner and decreased PD-induced MVD in the peritoneum. In conclusion, angiogenesis of the peritoneum induced by PD was inhibited using sTie2/Fc in a uremic rat model.
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Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver.
Arch. Toxicol.
PUBLISHED: 04-23-2013
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Several persistent organic pollutants are reported to be potentially associated with the risk of human diabetes that has become rapidly epidemic in China currently. 2,2,3,3,4,4,5,5,6,6-decabromodiphenyl ether (BDE209) is commercially most important both in the production and in the use of polybrominated diphenyl ethers (PBDEs). It might bioaccumulate in wildlife and human and is the only PBDEs mixture still used today. In the present study, male adult rats treated with BDE209 (0, 0.05, 1, and 20 mg/kg) for 8 weeks were used to explore the effects of BDE209 on glucose homeostasis and possible mechanisms; 0.05 mg/kg of BDE209 induced dose-related hyperglycemia. Then, we performed the full-genome gene expression microarrays, gene ontology analysis, and pathway analysis in this group and control. BDE209 induced 1,257 liver gene transcript changes, and 18 canonical pathways were significantly enriched. Four of them were involved in immune diseases, including autoimmune thyroid disease, graft-versus-host disease, allograft rejection, and type I diabetes mellitus (T1MD), which was confirmed by the decrease in serum insulin. Subsequently, gene act network and gene co-expression network found that some MHC molecules and TNF-? were involved in T1DM pathway, which was then confirmed by the increase in serum TNF-?. Additionally, reduced glutathione and superoxide dismutase in plasma indicated that oxidative damage might partly contribute to BDE209-induced hyperglycemia. The results of this study provide some new experimental evidence that the exposure to high levels of BDE209 may contribute to the onset of diabetes in human populations. Further work needs to be done to confirm this link.
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Long-term exposure to high particulate matter pollution and cardiovascular mortality: A 12-year cohort study in four cities in northern China.
Environ Int
PUBLISHED: 04-22-2013
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Epidemiologic studies have demonstrated that long-term exposure to relatively low levels of particulate air pollution is associated with adverse cardiovascular outcomes in Europe and North America. However, few studies have assessed the association with high level air pollutants. We aimed to assess the cardiovascular effects of long-term exposure to high level concentrations of inhalable particulate and to identify the characteristics of the Chinese population that are susceptible to the health effects. A retrospective cohort, containing 39,054 subjects from four cities in northern China, was followed for mortality of all cause and specific cardiovascular diseases from 1998 to 2009. Information on concentrations of PM10 (particulate matter<10?m in aerodynamic diameter) was collected from the local Environmental Monitoring Centers. The estimated exposure for the study participants was the mean concentration of PM10 over their surviving years during the cohort period. Relative risk values were obtained using Cox proportional hazards regression models after adjusting for potential confounding factors. For each 10?g/m(3) increase in PM10, the relative risk ratios (RRs) of all-cause mortality, cardiovascular disease mortality, ischemic heart disease mortality, heart failure disease mortality, and cerebrovascular disease mortality were 1.24 (95% CI, 1.22-1.27), 1.23 (95% CI, 1.19-1.26), 1.37 (95% CI, 1.28-1.47), 1.11(95% CI, 1.05-1.17), and 1.23(95% CI:1.18-1.28), respectively. Results from stratified analyses suggest that the effects of PM10 on cardiovascular mortality were more pronounced in males, smokers and people with a higher socioeconomic status. Long-term exposure to PM10 increases mortality from cardiovascular disease, especially from ischemic heart disease and this association seemed to be modified by other factors. Further research that focuses on exploring dose-response relationship and inter-population comparisons is warranted.
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[Analysis of three-dimensional fluorescence overlapping spectra using differential spectra and independent component analysis].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 04-17-2013
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The analysis of multi-component three-dimensional fluorescence overlapping spectra is always very difficult. In view of the advantage of differential spectra and based on the calculation principle of two-dimensional differential spectra, the three-dimensional fluorescence spectra with both excitation and emission spectra is fully utilized. Firstly, the excitation differential spectra and emission differential spectra are respectively computed after unfolding the three-dimensional fluorescence spectra. Then the excitation differential spectra and emission differential spectra of the single component are obtained by analyzing the multicomponent differential spectra using independent component analysis. In this process, the use of cubic spline increases the data points of excitation spectra, and the roughness penalty smoothing reduces the noise of emission spectra which is beneficial for the computation of differential spectra. The similarity indices between the standard spectra and recovered spectra show that independent component analysis based on differential spectra is more suitable for the component recognition of three-dimensional fluorescence overlapping spectra.
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Peripheral blood transcriptome sequencing reveals rejection-relevant genes in long-term heart transplantation.
Int. J. Cardiol.
PUBLISHED: 03-15-2013
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Peripheral blood-based gene expression patterns have been investigated as biomarkers to monitor the immune system and rule out rejection after heart transplantation. Recent advances in the high-throughput deep sequencing (HTS) technologies provide new leads in transcriptome analysis.
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Eculizumab and recurrent C3 glomerulonephritis.
Pediatr. Nephrol.
PUBLISHED: 03-01-2013
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Hyperactivity of the alternative complement pathway is the principle defect in C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease.
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Construction, expression, and characterization of thymosin alpha 1 tandem repeats in Escherichia coli.
Biomed Res Int
PUBLISHED: 02-28-2013
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Thymosin alpha 1 (T ? 1), which is composed of 28 amino acids, has been commercialized worldwide for its immune-modulatory and antitumor effects. T ? 1 can stimulate T cell proliferation and differentiation from bone marrow stem cells, augment cell-mediated immune responses, and regulate homeostasis of immune system. In this study, we developed a novel strategy to produce T ? 1 concatemer (T ? 1?) in Escherichia coli and compared its activity with chemically synthesized T ? 1. Results showed that T ? 1? can more effectively stimulate T cell proliferation and significantly upregulate IL-2 receptor expression. We concluded that the expression system for T ? 1 concatemer was constructed successfully, which could serve as an efficient tool for the production of large quantities of the active protein.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.