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Rapid synthesis of isoquinolinones by intramolecular coupling of amides and ketones.
Org. Biomol. Chem.
PUBLISHED: 11-20-2014
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Amides and ketones were intramolecularly coupled in the presence of KOt-Bu/DMF. The reaction provided good yields of a variety of isoquinolinones. A reaction mechanism of radical addition and subsequent E2-elimination is proposed.
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A novel frameshift mutation of epithelial sodium channel ?-subunit leads to Liddle syndrome in an isolated case.
Clin. Endocrinol. (Oxf)
PUBLISHED: 11-08-2014
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Liddle syndrome, an autosomal dominant form of monogenic hypertension, is attributed to mutations in the genes encoding ? and ? subunits (SCNN1B and SCNN1G) of the epithelial sodium channel (ENaC). The aim of this study was to search for pathogenic mutations of SCNN1B and SCNN1G in an adolescent under the impression of Liddle syndrome and no family history of hypertension.
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The stabilities and electronic structures of single-layer bismuth oxyhalides for photocatalytic water splitting.
Phys Chem Chem Phys
PUBLISHED: 10-29-2014
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The stabilities and electronic/band structures of single-layer bismuth oxyhalides have been investigated by employing first-principles calculations. The results indicate that the single-layer bismuth oxyhalide materials, except for BiOF, have robust energetic and dynamical stabilities because of their low formation energies and the absence of imaginary frequencies within the entire Brillouin zone. Furthermore, calculations of the electronic structures and optical absorptions indicate that single-layer BiOI possesses a favorable band gap, suitable band edge positions, different orbital characteristics and different effective masses at the valence band maximum (VBM) and conduction band minimum (CBM), thus presenting excellent photocatalytic activity for water splitting. Moreover, the resulting compressive strains can shift the band edge positions of the single-layer materials to more suitable places to enhance their photocatalytic activities.
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[Effect of climate change on net primary productivity of Korean pine (Pinus koraiensis) at different successional stages of broad-leaved Korean pine forest].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 10-28-2014
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Pinus koraiensis in broad-leaved Korean pine forests of Changbai Mountain at different successional stages (secondary poplar-birch forest, secondary coniferous and broad-leaved forest and the primitive Korean pine forest) were selected in this paper as the research objects. In this research, the annual growth of net primary productivity (NPP) (1921-2006) of P. koraiensis was obtained by combining the tree-ring chronology and relative growth formulae, the correlation between NPP of P. koraiensis and climatic factors was developed, and the annual growth of NPP of P. koraiensis at different successional stages in relation to climatic variation within different climate periods were analyzed. The results showed that, in the research period, the correlations between climatic factors and NPP of P. koraiensis at different successional stages were different. With increasing the temperature, the correlations between NPP of P. koraiensis in the secondary poplar-birch forest and the minimum temperatures of previous and current growing seasons changed from being significantly negative to being significantly positive. The positive correlation between NPP of P. koraiensis in the secondary coniferous and broad-leaved forest and the minimum temperature in current spring changed into significantly positive correlation between NPP of P. koraiensis and the temperatures in previous and current growing seasons. The climatic factors had a stronger hysteresis effect on NPP of P. koraiensis in the secondary coniferous and broad-leaved forest, but NPP of P. koraiensis in the primitive Korean pine forest had weaker correlation with temperature but stronger positive correlation with the precipitation of previous growing season. The increases of minimum and mean temperatures were obvious, but no significant variations of the maximum temperature and precipitation were observed at our site. The climatic variation facilitated the increase of the NPP of P. koraiensis in the secondary poplar-birch forest at the initial successional stage and in secondary coniferous and broad-leaved forest at the intermediate successional stage, and this effect was especially obvious for the secondary coniferous and broad-leaved forest, but very small for the primitive Korean pine forest which was at the climax phase.
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Effect of 1,25-dihydroxyvitamin d3 on regulatory T cells in ovariectomized mice.
Biomed. Environ. Sci.
PUBLISHED: 10-25-2014
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To investigate the correlation between regulatory T (Treg) cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in relation to Treg cells.
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Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs.
RNA
PUBLISHED: 10-21-2014
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The TATA box represents one of the most prevalent core promoters where the pre-initiation complexes (PICs) for gene transcription are assembled. This assembly is crucial for transcription initiation and well regulated. Here we show that some cellular microRNAs (miRNAs) are associated with RNA polymerase II (Pol II) and TATA box-binding protein (TBP) in human peripheral blood mononuclear cells (PBMCs). Among them, let-7i sequence specifically binds to the TATA-box motif of interleukin-2 (IL-2) gene and elevates IL-2 mRNA and protein production in CD4(+) T-lymphocytes in vitro and in vivo. Through direct interaction with the TATA-box motif, let-7i facilitates the PIC assembly and transcription initiation of IL-2 promoter. Several other cellular miRNAs, such as mir-138, mir-92a or mir-181d, also enhance the promoter activities via binding to the TATA-box motifs of insulin, calcitonin or c-myc, respectively. In agreement with the finding that an HIV-1-encoded miRNA could enhance viral replication through targeting the viral promoter TATA-box motif, our data demonstrate that the interaction with core transcription machinery is a novel mechanism for miRNAs to regulate gene expression.
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A Gain-of-Function Mutation in Tnni2 Impeded Bone Development through Increasing Hif3a Expression in DA2B Mice.
PLoS Genet.
PUBLISHED: 10-01-2014
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Distal arthrogryposis type 2B (DA2B) is an important genetic disorder in humans. However, the mechanisms governing this disease are not clearly understood. In this study, we generated knock-in mice carrying a DA2B mutation (K175del) in troponin I type 2 (skeletal, fast) (TNNI2), which encodes a fast-twitch skeletal muscle protein. Tnni2K175del mice (referred to as DA2B mice) showed typical DA2B phenotypes, including limb abnormality and small body size. However, the current knowledge concerning TNNI2 could not explain the small body phenotype of DA2B mice. We found that Tnni2 was expressed in the osteoblasts and chondrocytes of long bone growth plates. Expression profile analysis using radii and ulnae demonstrated that Hif3a expression was significantly increased in the Tnni2K175del mice. Chromatin immunoprecipitation assays indicated that both wild-type and mutant tnni2 protein can bind to the Hif3a promoter using mouse primary osteoblasts. Moreover, we showed that the mutant tnni2 protein had a higher capacity to transactivate Hif3a than the wild-type protein. The increased amount of hif3a resulted in impairment of angiogenesis, delay in endochondral ossification, and decrease in chondrocyte differentiation and osteoblast proliferation, suggesting that hif3a counteracted hif1a-induced Vegf expression in DA2B mice. Together, our data indicated that Tnni2K175del mutation led to abnormally increased hif3a and decreased vegf in bone, which explain, at least in part, the small body size of Tnni2K175del mice. Furthermore, our findings revealed a new function of tnni2 in the regulation of bone development, and the study of gain-of-function mutation in Tnni2 in transgenic mice opens a new avenue to understand the pathological mechanism of human DA2B disorder.
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The complete mitochondrial genome of Vespertilio sinensis from China.
Mitochondrial DNA
PUBLISHED: 09-23-2014
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Abstract The complete mitogenome sequence of Vespertilio sinensis was determined using long PCR. The genome was 17,146?bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 control region. The overall base composition of the heavy strand is A (32.73%), C (23.64%), T (29.72%), and G (13.91%). The base compositions present clearly the A-T skew, which is most obviously in the control region and protein-coding genes. The extended termination-associated sequence domain, the central conserved domain and the conserved sequence block domain are defined in the mitochondrial genome control region of V. sinensis.
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Direct inter- and intramolecular addition of amides to arylalkenes promoted by KOt-Bu/DMF.
J. Org. Chem.
PUBLISHED: 09-10-2014
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Direct addition of tetrahydroisoquinoline derived amides to arylalkenes has been achieved in the presence of KOt-Bu/DMF. Both intermolecular and intramolecular reactions could occur in good yields. ?-Amido alkyl radicals are proposed to be generated under the reaction conditions. The reaction is efficient for the synthesis of seven-membered nitrogen heterocycles. A homoprotoberberine was prepared conveniently via this method.
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Chlorogenic acid protects against atherosclerosis in ApoE-/- mice and promotes cholesterol efflux from RAW264.7 macrophages.
PLoS ONE
PUBLISHED: 09-04-2014
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Chlorogenic acid (CGA) is one of the most abundant polyphenols in the human diet and is suggested to be a potential antiatherosclerotic agent due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate the effect of CGA on atherosclerosis development in ApoE(-/-) mice and its potential mechanism. ApoE(-/-) mice were fed a cholesterol-rich diet without (control) or with CGA (200 and 400 mg/kg) or atorvastatin (4 mg/kg) for 12 weeks. During the study plasma lipid and inflammatory parameters were determined. Treatment with CGA (400 mg/kg) reduced atherosclerotic lesion area and vascular dilatation in the aortic root, comparable to atorvastatin. CGA (400 mg/kg) also significantly decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol as well as inflammatory markers. Supplementation with CGA or CGA metabolites-containing serum suppressed oxidized low-density lipoprotein (oxLDL)-induced lipid accumulation and stimulated cholesterol efflux from RAW264.7 cells. CGA significantly increased the mRNA levels of PPAR?, LXR?, ABCA1 and ABCG1 as well as the transcriptional activity of PPAR?. Cholesterol efflux assay showed that three major metabolites, caffeic, ferulic and gallic acids, significantly stimulated cholesterol efflux from RAW264.7 cells. These results suggest that CGA potently reduces atherosclerosis development in ApoE(-/-) mice and promotes cholesterol efflux from RAW264.7 macrophages. Caffeic, ferulic and gallic acids may be the potential active compounds accounting for the in vivo effect of CGA.
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A novel signal transduction pathway that modulates rhl quorum sensing and bacterial virulence in Pseudomonas aeruginosa.
PLoS Pathog.
PUBLISHED: 08-28-2014
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The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activation of its cognate response regulator BfmR, which in turn directly binds to the promoter and decreases the expression of the rhlR gene that encodes the QS regulator RhlR, causing the inhibition of the rhl QS system. In the absence of bfmS, the Acka-Pta pathway can modulate the regulatory activity of BfmR. In addition, BfmS tunes the expression of 202 genes that comprise 3.6% of the P. aeruginosa genome. We further demonstrate that deletion of bfmS causes substantially reduced virulence in lettuce leaf, reduced cytotoxicity, enhanced invasion, and reduced bacterial survival during acute mouse lung infection. Intriguingly, specific missense mutations, which occur naturally in the bfmS gene in P. aeruginosa cystic fibrosis (CF) isolates such as DK2 strains and RP73 strain, can produce BfmS variants (BfmSL181P, BfmSL181P/E376Q, and BfmSR393H) that no longer repress, but instead activate BfmR. As a result, BfmS variants, but not the wild-type BfmS, inhibit the rhl QS system. This study thus uncovers a previously unexplored signal transduction pathway, BfmS/BfmR/RhlR, for the regulation of rhl QS in P. aeruginosa. We propose that BfmRS TCS may have an important role in the regulation and evolution of P. aeruginosa virulence during chronic infection in CF lungs.
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DNA methylation dynamics during ex vivo differentiation and maturation of human dendritic cells.
Epigenetics Chromatin
PUBLISHED: 08-20-2014
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Dendritic cells (DCs) are important mediators of innate and adaptive immune responses, but the gene networks governing their lineage differentiation and maturation are poorly understood. To gain insight into the mechanisms that promote human DC differentiation and contribute to the acquisition of their functional phenotypes, we performed genome-wide base-resolution mapping of 5-methylcytosine in purified monocytes and in monocyte-derived immature and mature DCs.
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[Holstein-Friesian RBC as human blood substitute].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 08-19-2014
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?-Gal, the main xenotransplantation antigen, can lead to hyperacute rejection (HAR) in xenotransplantation. This study was purposed to investigate the effect of recombinant ?-galactosidase (?-Gal antigen) on the Holstein-Friesian(H-F) red blood cells (RBC). The enzymelysis method was used to digest the ?-Gal antigen on H-F RBC; the saline and anti-human globulin methods were used to perform the agglutination test of H-F RBC and human plasma; the flow cytometry was used to detect the ?-Gal antigen on surface of H-F RBC, fluorescence intensity of FITC-IB4 and FITC-IgG labeled RBC. The results indicated that the saline and anti-human globulin method showed ?-galactosidase-treated H-F RBC fail to agglutinate with human pooled plasma; the flow cytometry showed the fluorescence intensity of FITC-IB4 and FITC-IgG labled RBC decrease 99.0% and 87.8%, respectively. It is concluded that the novel ?-galactosidase can be used to cleared the ?-Gal antigen on the surface of H-F RBC and ?-galactosidase-treated H-F RBC may be considered as human blood substitute.
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Composite photothermal platform of polypyrrole-enveloped Fe?O? nanoparticle self-assembled superstructures.
ACS Appl Mater Interfaces
PUBLISHED: 08-18-2014
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Photothermal nanoplatforms with small size, low cost, multifunctionality, good biocompatibility and in particular biodegradability are greatly desired in the exploration of novel diagnostic and therapeutic methodologies. Despite Fe3O4 nanoparticles (NPs) have been approved as safe clinical agents, the low molar extinction coefficient and subsequent poor photothermal performance shed the doubt as effective photothermal materials. In this paper, we demonstrate the fabrication of polypyrrole (PPy)-enveloped Fe3O4 NP superstructures with a spherical morphology, which leads to a 300-fold increase in the molar extinction coefficient. The basic idea is the optimization of Fe3O4 electronic structures. By controlling the self-assembly of Fe3O4 NPs, the diameters of the superstructures are tuned from 32 to 64 nm. This significantly enhances the indirect transition and magnetic coupling of Fe ions, thus increasing the molar extinction coefficient of Fe3O4 NPs from 3.65 × 10(6) to 1.31 × 10(8) M(-1) cm(-1) at 808 nm. The envelopment of Fe3O4 superstructures with conductive PPy shell introduces additional electrons in the Fe3O4 oscillation system, and therewith further enhances the molar extinction coefficient to 1.12 × 10(9) M(-1) cm(-1). As a result, the photothermal performance is greatly improved. Primary cell experiments indicate that PPy-enveloped Fe3O4 NP superstructures are low toxic, and capable to kill Hela cells under near-infrared laser irradiation. Owing to the low cost, good biocompatibility and biodegradability, the PPy-enveloped Fe3O4 NP superstructures are promising photothermal platform for establishing novel diagnostic and therapeutic methods.
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TEMPORARY REMOVAL: Challenges and cautions with small and retrospective postoperative pain genome wide association studies with TAOK3.
Pain
PUBLISHED: 08-17-2014
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The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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Myeloid-specific disruption of tyrosine phosphatase Shp2 promotes alternative activation of macrophages and predisposes mice to pulmonary fibrosis.
J. Immunol.
PUBLISHED: 08-15-2014
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The alternative activation of M2 macrophages in the lungs has been implicated as a causative agent in pulmonary fibrosis; however, the mechanisms underlying M2 polarization are poorly characterized. In this study, we investigated the role of the ubiquitously expressed Src homology domain-containing tyrosine phosphatase Shp2 in this process. Shp2 inactivation augmented IL-4-mediated M2 polarization in vitro, suggesting that Shp2 regulates macrophage skewing and prevents a bias toward the M2 phenotype. Conditional removal of Shp2 in monocytes/macrophages with lysozyme M promoter-driven Cre recombinase caused an IL-4-mediated shift toward M2 polarization. Additionally, an increase in arginase activity was detected in Shp2(?/?) mice after i.p. injection of chitin, whereas Shp2-deficient macrophages showed enhanced M2 polarization and protection against schistosome egg-induced schistosomiasis. Furthermore, mutants were more sensitive than control mice to bleomycin-induced inflammation and pulmonary fibrosis. Shp2 was associated with IL-4R? and inhibited JAK1/STAT6 signaling through its phosphatase activity; loss of Shp2 promoted the association of JAK1 with IL-4R?, which enhanced IL-4-mediated JAK1/STAT6 activation that resulted in M2 skewing. Taken together, these findings define a role for Shp2 in alveolar macrophages and reveal that Shp2 is required to inhibit the progression of M2-associated pulmonary fibrosis.
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Silymarin Attenuates Airway Inflammation Induced by Cigarette Smoke in Mice.
Inflammation
PUBLISHED: 08-13-2014
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Cigarette smoke (CS), which increases inflammation and oxidative stress, is a major risk factor for the development of COPD. In this study, we investigated the effects of silymarin, a polyphenolic flavonoid isolated from the seeds and fruits of milk thistle, on CS-induced airway inflammation and oxidative stress in mice and the possible mechanisms. BALB/c mice were exposed to CS for 2 h twice daily, 6 days per week for 4 weeks. Silymarin (25, 50 mg/kg?·?day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and the detection of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination, myeloperoxidase (MPO) activity assay, superoxide dismutase (SOD) activities, and malondialdehyde (MDA) levels. The phosphorylation of ERK and p38 was evaluated by Western blotting. Pretreatment with silymarin significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction. The numbers of total cells, macrophages, and neutrophils, along with the MPO activity (a marker of neutrophil accumulation) in BALF, were remarkably decreased by silymarin in CS-exposed mice (all p?
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MicroRNA-mediated repression of nonsense mRNAs.
Elife
PUBLISHED: 08-08-2014
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Numerous studies have established important roles for microRNAs (miRNAs) in regulating gene expression. Here, we report that miRNAs also serve as a surveillance system to repress the expression of nonsense mRNAs that may produce harmful truncated proteins. Upon recognition of the premature termination codon by the translating ribosome, the downstream portion of the coding region of an mRNA is redefined as part of the 3' untranslated region; as a result, the miRNA-responsive elements embedded in this region can be detected by miRNAs, triggering accelerated mRNA deadenylation and translational inhibition. We demonstrate that naturally occurring cancer-causing APC (adenomatous polyposis coli) nonsense mutants which escape nonsense-mediated mRNA decay (NMD) are repressed by miRNA-mediated surveillance. In addition, we show that miRNA-mediated surveillance and exon-exon junction complex-mediated NMD are not mutually exclusive and act additively to enhance the repressive activity. Therefore, we have uncovered a new role for miRNAs in repressing nonsense mutant mRNAs.
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Predictive value of fetal lung volume in prenatally diagnosed skeletal dysplasia.
Prenat. Diagn.
PUBLISHED: 08-08-2014
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Pulmonary hypoplasia is a major cause of death in lethal skeletal dysplasias. We hypothesize that in fetuses with prenatally diagnosed skeletal dysplasia, comparison of observed-to-expected (O/E) lung volume will help predict lethality.
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[Resonance raman spectra of linear polymer molecule].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-07-2014
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The present paper summarizes the characteristics of resonance Raman spectra of the linear polymer molecule, and its relations with the molecular structure, including: electronic spectra(ultraviolet-visible absorption spectrum), Raman spectra characteristics and its relations with external field; Modulation relation between the electron energy gap and CC atom vibration; Several experimental results were obtained: The UV-visible absorption spectra are red-shifted with decreasing temperature, increasing solvent density and reducing solution concentration, and because the linear polymer molecule has high structured order, decreasing pi electron energy gap; extended pi electronic delocalization, large effective conjugation length, large intensity of the Raman activity, Ramrnan spectrum are red-shifted, with large scattering cross section. "Am plitude modes" are the ideal theory models to study the linear polymer molecule.
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Six-Coordinate Lanthanide Complexes: Slow Relaxation of Magnetization in the Dysprosium(III) Complex.
Chemistry
PUBLISHED: 07-25-2014
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A series of six-coordinate lanthanide complexes {(H3 O)[Ln(NA)2 ]?H2 O}n (H2 NA=5-hydroxynicotinic acid; Ln=Gd(III) (1?Gd); Tb(III) (2?Tb); Dy(III) (3?Dy); Ho(III) (4?Ho)) have been synthesized from aqueous solution and fully characterized. Slow relaxation of the magnetization was observed in 3?Dy. To suppress the quantum tunneling of the magnetization, 3?Dy diluted by diamagnetic Y(III) ions was also synthesized and magnetically studied. Interesting butterfly-like hysteresis loops and an enhanced energy barrier for the slow relaxation of magnetization were observed in diluted 3?Dy. The energy barrier (?? ) and pre-exponential factor (?0 ) of the diluted 3?Dy are 75?K and 4.21×10(-5) ?s, respectively. This work illustrates a successful way to obtain low-coordination-number lanthanide complexes by a framework approach to show single-ion-magnet-like behavior.
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[Alanine solution as enzyme reaction buffer used in A to O blood group conversion].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 07-04-2014
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The aim of this study was to investigate the effect of alanine solution as ?-N-acetylgalactosaminidase enzyme reaction buffer on the enzymatic activity of A antigen. The binding ability of ?-N-acetylgalactosaminidase with RBC in different reaction buffer such as alanine solution, glycine solution, normal saline (0.9% NaCl), PBS, PCS was detected by Western blot. The results showed that the efficiency of A to O conversion in alanine solution was similar to that in glycine solution, and Western blot confirmed that most of enzymes binded with RBC in glycine or alanine solution, but few enzymes binded with RBC in PBS, PCS or normal saline. The evidences indicated that binding of enzyme with RBC was a key element for A to O blood group conversion, while the binding ability of ?-N-acetylgalactosaminidase with RBC in alanine or glycine solution was similar. It is concluded that alanine solution can be used as enzyme reaction buffer in A to O blood group conversion. In this buffer, the ?-N-acetylgalactosaminidase is closely binded with RBC and ?-N-acetylgalactosaminidase plays efficient enzymatic activity of A antigen.
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A general approach to antibody thermostabilization.
MAbs
PUBLISHED: 07-02-2014
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Antibody engineering to enhance thermostability may enable further application and ease of use of antibodies across a number of different areas. A modified human IgG framework has been developed through a combination of engineering approaches, which can be used to stabilize antibodies of diverse specificity. This is achieved through a combination of complementarity-determining region (CDR)-grafting onto the stable framework, mammalian cell display and in vitro somatic hypermutation (SHM). This approach allows both stabilization and maturation to affinities beyond those of the original antibody, as shown by the stabilization of an anti-HA33 antibody by approximately 10°C and affinity maturation of approximately 300-fold over the original antibody. Specificities of 10 antibodies of diverse origin were successfully transferred to the stable framework through CDR-grafting, with 8 of these successfully stabilized, including the therapeutic antibodies adalimumab, stabilized by 9.9°C, denosumab, stabilized by 7°C, cetuximab stabilized by 6.9°C and to a lesser extent trastuzumab stabilized by 0.8°C. This data suggests that this approach may be broadly useful for improving the biophysical characteristics of antibodies across a number of applications.
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[Identification of a pathogenic microduplication in a Chinese split-hand/split-foot malformation family].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 06-15-2014
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OBJECTIVE To identify the potential pathogenic mutation in a Chinese family with split hand/foot malformation (SHFM). METHODS Affymetrix SNP 6.0 array was used to perform a genome-wide copy number variations scan, and quantitative real-time PCR (qPCR) was applied to validate the identified genomic duplication. RESULTS A ~560 kb microduplication on the chromosome 10q24 was identified. The qPCR assay confirmed the presence of this microduplication in all the available affected family members. CONCLUSION The ~560 kb microduplication is probably the pathogenic mutation underlying the SHFM phenotype in the studied family.
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Rhodium(III)-catalyzed intramolecular amidoarylation and hydroarylation of alkyne via C-H activation: switchable synthesis of 3,4-fused tricyclic indoles and chromans.
Chem. Commun. (Camb.)
PUBLISHED: 05-30-2014
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The controllable intramolecular amidoarylation and hydroarylation of alkynes has been achieved via rhodium(III)-catalyzed C-H activation. The merger of two distinct reaction pathways allows for the development of atom- and step-economic protocols for the switchable synthesis of 3,4-fused indoles and chromans, respectively.
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A versatile complementation assay for cell-to-cell and long distance movements by cucumber mosaic virus based agro-infiltration.
Virus Res.
PUBLISHED: 05-26-2014
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Microinjection, bombardment or tobamovirus and potexvirus based assay has been developed to identify the putative movement protein (MP) or to characterize plasmodesma-mediated macromolecular transport. In this study, we developed a versatile complementation assay for the cell-to-cell and long distance movements of macromolecules by agro-infiltration based on the infectious clones of cucumber mosaic virus (CMV). The movement-deficient CMV reporter was constructed by replacing the MP on RNA 3 with ER targeted GFP. The ectopic expression of CMV MP was able to efficiently move the RNA3-MP::erGFP reporter from the original cell to neighboring cells, whereas CMV MP-M5 mutant was unable to initiate the movement. Importantly, the presence of CMV RNA1 and RNA2 can dramatically amplify the movement signals once the RNA3-MP::erGFP reporter moves out of the original cell. The appropriate observation time for this movement complementation assay was at 48-72 hours post infiltration (hpi), whereas the optimal incubation temperature was between 25 and 28 °C. The ectopic co-expression of MPs from other virus genera, NSm from tomato spotted wilt tospovirus (TSWV) or NSvc4 from rice stripe tenuivirus (RSV), could also facilitate the movement of the RNA3::erGFP reporter from the original cell into other cells. The chimeric mutant virus created by substituting the MP of CMV RNA3 with NSm from TSWV or NSvc4 from RSV move systemically in Nicotiana benthamiana plants by agro-infiltration. This agro-infiltration complementation assay is simple, efficient and reliable. Our approach provides an alternative and powerful tool with great potentials in identifying putative movement protein and characterizing macromolecular trafficking.
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One-dose vaccination associated with attenuated disease severity of adolescent and adult varicella cases in Beijing's Fengtai District.
Hum Vaccin Immunother
PUBLISHED: 05-22-2014
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Background In recent years, the number of varicella cases in adults has significantly increased in Beijing. However, the effect of the vaccination on varicella-related characteristics among adults has not been studied. Methods and Results: Using data from the Infectious Disease Reporting System and the Immunization Information System, we compared the epidemiology and disease severity in breakthrough and unvaccinated varicella cases in adolescents and adults (? 15 year-old) from 2008 to 2011 in Beijing's Fengtai district, China. The results showed that the age (P = 0.003),contact history (90% vs. 73%, P = 0.019) and outbreak cases (10% vs. 1%, P<0.0001) were significantly differently distributed between the two groups and that both the incidence of moderate-to-severe cases (26% vs. 45%, P = 0.035, OR = 0.446) and varicella-associated fever (49% vs. 66%, P = 0.068, OR = 0.534) were either significantly lower or trended to be lower in the breakthrough group than in the unvaccinated group. Additionally,vaccine effectiveness against moderate-to-severe cases of varicella was 55.4%. Conclusion: Altogether, these results indicate that vaccination against varicella among adolescents and adults affected the epidemiology and attenuated the disease severity of the cases. The Results from this study will provide useful information for the prevention of varicella in adolescents and adults.
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[Trend and outcome of multiple pregnancies in Beijing, 1996-2010].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 05-17-2014
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To describe the trend of multiple pregnancies and to compare the results with single pregnancy in Beijing from 1996 to 2010. Prevalence rates of pregnancy complications were compared between multiple and single pregnancies.
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[Effect of electroacupuncture intervention at different time-points of post-modeling on hippocampal monoamine neurotransmitter levels in mice with vascular dementia].
Zhen Ci Yan Jiu
PUBLISHED: 05-14-2014
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To observe the effect of electrocupuncture (EA) intervention at different time-points of post-modeling on behavior and hippocampal monoamine neurotransmitter noradrenalin (NE), dopamine (DA) and 5-hydroxytrypamine (5-HT) contents in vascular dementia (VD) mice, so as to study its mechanism underlying improvement of VD.
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Growth factor receptor bound protein 2-associated binder 2, a scaffolding adaptor protein, negatively regulates host immunity against tuberculosis.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 05-09-2014
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Cell-mediated immunity is indispensable for host protection against tuberculosis (TB). Growth factor receptor bound protein 2-associated binder (Gab) 2, a scaffolding adaptor protein, negatively regulates signaling pathways critical for T cell-mediated immunity. We sought to investigate the clinical significance and immunological role of Gab2 in Mycobacterium tuberculosis infection. We evaluated Gab2 protein and messenger RNA (mRNA) expression in human patients with pulmonary TB and determined the correlation of the mRNA expression pattern with antigen-specific IFN-? secretion. Subsequently, we carried out M. tuberculosis infection in Gab2-deficient and wild-type control mice to explore the immunological role of Gab2 by examining bacterial load, histological changes, cytokine secretion, and gene expression of immune-associated transcription factors. mRNA levels of Gab2 and its correlated family member, Gab1, were markedly decreased in untreated patients with pulmonary TB compared with healthy control subjects. Importantly, this decreased Gab2 expression to normal levels after bacterial load in the patient's sputum became undetectable under the standard anti-TB treatment, which negatively correlated with the level of M. tuberculosis antigen-specific IFN-? secretion. In the M. tuberculosis infection mouse model, infected Gab2-deficient mice exhibited decreased bacterial load and milder lung pathological damage compared with infected wild-type mice, accompanied by decreased production of IL-2, IL-6, and granulocyte/macrophage colony-stimulating factor proinflammatory cytokines, and an increased T-cell-specific T-box transcription factor/GATA binding protein 3 expression ratio. Overall, our study indicates that down-regulation of Gab2 relates to a protective function during M. tuberculosis infection, revealing a potential negative regulatory role for Gab2 in immunity to TB.
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Polypyrrole-coated chainlike gold nanoparticle architectures with the 808 nm photothermal transduction efficiency up to 70%.
ACS Appl Mater Interfaces
PUBLISHED: 04-04-2014
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Aqueous Au nanoparticles (NPs) are employed as the building blocks to construct chainlike self-assembly architectures, which greatly enhance the photothermal performance at 808 nm. Biocompatible polypyrrole (PPy) is further adopted as the package material to coat Au NP chains, producing stable photothermal agents. As a result of contributions from chainlike Au, the PPy shell, as well as the Au-PPy composite structures, the capability of photothermal transduction at 808 nm is greatly enhanced, represented by the high photothermal transduction efficiency up to 70%. Primary animal experiment proves that the current composite photothermal agents are efficient in inhibiting tumor growth under an 808 nm irradiation, showing the potentials for in vivo photothermal therapy.
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The Effects of Lycopene on the Methylation of the GSTP1 Promoter and Global Methylation in Prostatic Cancer Cell Lines PC3 and LNCaP.
Int J Endocrinol
PUBLISHED: 03-28-2014
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DNA (cytosine-5-) methylation silencing of GSTP1 function occurs in prostate adenocarcinoma (PCa). Previous studies have shown that there is an inverse relationship between dietary lycopene intake and the risk of PCa. However, it is unknown whether lycopene reactivates the tumor suppressor gene glutathioneS-transferase-? (GSTP1) by demethylation of the hypermethylated CpGs that act to silence the GSTP1 promoter. Here, we demonstrated that lycopene treatment significantly decreased the methylation levels of the GSTP1 promoter and increased the mRNA and protein levels of GSTP1 in an androgen-independent PC-3 cell line. In contrast, lycopene treatment did not demethylate the GSTP1 promoter or increase GSTP1 expression in the androgen-dependent LNCaP cell line. DNA methyltransferase (DNMT) 3A protein levels were downregulated in PC-3 cells following lycopene treatment; however, DNMT1 and DNMT3B levels were unchanged. Furthermore, the long interspersed element (LINE-1) and short interspersed element ALU were not demethylated when treated by lycopene. In LNCaP cells, lycopene treatment did not affect any detected DNMT protein expression, and the methylation levels of LINE-1 and ALU were decreased. These results indicated that the protective effect of lycopene on the prostate is different between androgen-dependent and androgen-independent derived PCa cells. Further, in vivo studies should be conducted to confirm these promising results and to evaluate the potential role of lycopene in the protection of the prostate.
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The epidemiology of varicella cases among children in Beijing's Fengtai District from 2008 to 2012.
Vaccine
PUBLISHED: 03-24-2014
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In recent years, the number of breakthrough cases of varicella (onset >42 days after vaccination) increased each year, and varicella outbreaks continue to occur in Beijing. Data from the Immunization Information System and the Infectious Disease Reporting System demonstrated that in Beijing's Fengtai District, the varicella breakthrough rate increased from 0.7% in 2008 to 2.5% in 2012 and showed an increased trend (P<0.001). Among the varicella cases in children (age of 3-15 years), the number of breakthrough cases increased from 167 in 2008 to 622 in 2012, which was 45.2% (n=1735) of the total child cases (n=3842). From 2008 to 2012, a total of 62 outbreaks occurred; among the 787 affected child outbreak cases, 61% were vaccinated. Altogether, the results from this study indicated that 1-dose vaccination cannot sufficiently prevent the occurrence of breakthrough cases of varicella or control varicella outbreaks in Beijing's Fengtai District.
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The caffeoylquinic acid-rich Pandanus tectorius fruit extract increases insulin sensitivity and regulates hepatic glucose and lipid metabolism in diabetic db/db mice.
J. Nutr. Biochem.
PUBLISHED: 03-18-2014
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Caffeoylquinic acids (CQAs) are widely distributed in various foods. While some CQAs have been shown to possess antihyperglycemic activities, whether it is beneficial for diabetes patients to ingest CQA-rich foods has still to be known. In this work, the antihyperglycemic and antihyperlipidemic effects of CQA-rich Pandanus tectorius fruit extract (PTF) was investigated in diabetic db/db mice. Treatment with PTF (200 mg/kg) significantly decreased body weight and fasting glucose level, alleviated hyperinsulinism and hyperlipidemia and declined glucose area under the curve in oral glucose tolerance test and insulin tolerance test. The elevated levels of serum proinflammatory cytokines and islet hypertrophy in db/db mice were remarkably attenuated by PTF treatment. Biochemical analysis showed that administration of PTF significantly stimulated the phosphorylation of AMP-activated protein kinase (AMPK) and Akt substract of 160 kDa (AS160), and enhanced the expression and translocation of glucose transporter type 4 (GLUT4) in skeletal muscles. It also increased the activity of hexokinase, decreased the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase and switched the transcription of several key lipid metabolic genes in the liver, which, in turn, improved hepatic glucose and lipid profiles as determined by nuclear magnetic resonance-based metabolomics. Overall, the CQA-rich PTF is beneficial for the treatment of diabetes. It may alleviate hyperglycemia and dyslipidemia via activation of AMPK-AS160-GLUT4 pathway in skeletal muscles and inhibition of gluconeogenesis and lipogenesis in the liver.
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Removal of effluent dissolved organic matter of different molecular sizes by advanced treatments and soil infiltration.
Water Environ. Res.
PUBLISHED: 03-13-2014
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Removal of municipal effluent-derived dissolved organic matter (DOM) of various apparent molecular weights (AMWs) was compared among ozonation, nanofiltration, ultrafiltration, and magnetic ion exchange (MIEX) resin coagulation. These advanced technologies were applied as pretreatments for soil aquifer treatment (SAT). Soil aquifer treatment alone removed 20 to 30% of dissolved organic carbon (DOC) and UV254. Soil aquifer treatment effectively removed 100% and 76% of DOM with AMWs of 21.3 to 31.6 kDa and 0.4 to 1.0 kDa, respectively. With pretreatments of ozonation, MIEX resin coagulation and nanofiltration, substantially higher removals (40 to 75%) were achieved for DOC and UV254. The removal efficiency of the entire system decreased as nanofiltration-SAT > ozonation-SAT > MIEX-SAT > ultrafiltration-SAT, which is positively related to the removal efficiency for medium AMW (1.8 to 7.7 kDa, mainly humic substances) DOM during pretreatments. Different pretreatments should, therefore, be chosen in accordance with the water quality of feed water and water products and SAT removal efficiency.
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Secular trends of low birthweight and macrosomia and related maternal factors in Beijing, China: a longitudinal trend analysis.
BMC Pregnancy Childbirth
PUBLISHED: 03-11-2014
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Information tracking changes of birthweight is scarce in China. To examine trends of low birthweight (birthweight < 2500 g) and macrosomia (birthweight ? 4000 g) and potential risk factors in Beijing, hospital records from two major obstetrics and gynecology hospitals in urban districts in Beijing were analyzed.
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Low junctional adhesion molecule A expression correlates with poor prognosis in gastric cancer.
J. Surg. Res.
PUBLISHED: 03-07-2014
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The aberrant expression of junctional adhesion molecule A (JAM-A), which has a close correlation with the development, progression, metastasis, and prognosis of cancer, has been frequently reported. However, neither JAM-A expression nor its correlation with clinicopathologic variables and patient survival has been defined in gastric cancers. Moreover, little is known about the role of JAM-A in gastric cancer progression. We carried out the present study to investigate the prognostic value of JAM-A expression in gastric cancer patients. Furthermore, the biological roles of JAM-A in gastric cancer progression were also investigated.
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Kinetics and quantitative structure-activity relationship study on the degradation reaction from perfluorooctanoic acid to trifluoroacetic acid.
Int J Mol Sci
PUBLISHED: 03-01-2014
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Investigation of the degradation kinetics of perfluorooctanoic acid (PFOA) has been carried out to calculate rate constants of the main elementary reactions using the multichannel Rice-Ramsperger-Kassel-Marcus theory and canonical variational transition state theory with small-curvature tunneling correction over a temperature range of 200~500 K. The Arrhenius equations of rate constants of elementary reactions are fitted. The decarboxylation is role step in the degradation mechanism of PFOA. For the perfluorinated carboxylic acids from perfluorooctanoic acid to trifluoroacetic acid, the quantitative structure-activity relationship of the decarboxylation was analyzed with the genetic function approximation method and the structure-activity model was constructed. The main parameters governing rate constants of the decarboxylation reaction from the eight-carbon chain to the two-carbon chain were obtained. As the structure-activity model shows, the bond length and energy of C1-C2 (RC1-C2 and EC1-C2) are positively correlated to rate constants, while the volume (V), the energy difference between EHOMO and ELUMO (?E), and the net atomic charges on atom C2 (QC2) are negatively correlated.
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Studies on [PtCl2 ]- or [AuCl]-catalyzed cyclization of 1-(Indol-2-yl)-2,3-allenols: the effects of water/steric hindrance and 1,2-migration selectivity.
Chemistry
PUBLISHED: 02-28-2014
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The [PtCl2 ]- or [AuCl]-catalyzed reaction of 1-(indol-2-yl)-2,3-allenols occurred smoothly at room temperature to afford a series of poly-substituted carbazoles efficiently. Compared with the [PtCl2 ]-catalyzed process, the [AuCl]-catalyzed reaction represents a significant advance in terms of the scope and the selectivity. Selective 1,2-alkyl or aryl migration of the gold carbene intermediate was observed: compared with the methyl group, the isopropyl, cyclopropyl, cyclobutyl, and cyclohexyl groups migrate exclusively; the cyclopropyl group shifts selectively over the ethyl group; the 1,2-migration of a non-methyl linear alkyl is faster than methyl group; the phenyl group migrates exclusively over methyl or ethyl group. DFT calculations show that water makes the elimination of H2 O facile requiring a much lower energy and validates the migratory preferences of different alkyl or phenyl groups observed.
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Isoflavones Extracted from Chickpea Cicer arietinum L. Sprouts Induce Mitochondria-Dependent Apoptosis in Human Breast Cancer Cells.
Phytother Res
PUBLISHED: 02-24-2014
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Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation-7 (MCF-7). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that ICS (10-60?µg/mL) significantly inhibited the proliferation of both cell lines in a time-dependent and dose-dependent fashion. Wright-Giemsa staining as well as annexin V-fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose-dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis-promoting gene Bcl-2-associated X protein and decreased the expression of the antiapoptotic gene Bcl-2. Western blot analysis showed that treatment of SKBr3 and MCF-7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose-dependent manner. Flow cytometry assays using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide showed a dose-dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose-dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.
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Peptide deformylase inhibitor actinonin reduces celastrol's HSP70 induction while synergizing proliferation inhibition in tumor cells.
BMC Cancer
PUBLISHED: 02-24-2014
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Celastrol is a promising anti-tumor agent, yet it also elevates heat shock proteins (HSPs), especially HSP70, this effect believed to reduce its anti-tumor effects. Concurrent use of siRNA to increase celastrol's anti-tumor effects through HSP70 interference has been reported, but because siRNA technology is difficult to clinically apply, an alternative way to curb unwanted HSP70 elevation caused by celastrol treatment is worth exploring.
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Methyl salicylate lactoside inhibits inflammatory response of fibroblast-like synoviocytes and joint destruction in collagen-induced arthritis in mice.
Br. J. Pharmacol.
PUBLISHED: 02-23-2014
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Methyl salicylate 2-O-?-d-lactoside (MSL), whose chemical structure is similar to that of salicylic acid, is a natural product derivative isolated from a traditional Chinese herb. The aim of this study was to investigate the therapeutic effect of MSL in mice with collagen-induced arthritis (CIA) and explore its underlying mechanism.
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Bone marrow-derived mesenchymal stem cells protect against lung injury in a mouse model of bronchopulmonary dysplasia.
Mol Med Rep
PUBLISHED: 02-14-2014
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The aim of the present study was to investigate the effect of bone marrow?derived mesenchymal stem cells (BMSCs) in the treatment of lung injury in a mouse model of bronchopulmonary dysplasia (BPD) and examine the underlying mechanisms. A mouse model of BPD was created using continuous exposure to high oxygen levels for 14 days. BMSCs were isolated, cultured and then labeled with green fluorescent protein. Cells (1x106) were subsequently injected intravenously 1 h prior to high oxygen treatment. Animals were randomly divided into three groups (n=5 in each): Control group, BPD model group and BMSC injection group. At two weeks post?treatment, the expression of transforming growth factor??1 (TGF??1), vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF) was detected using immunohistochemical staining and immunofluorescence. Compared with the BPD model group, the body weight, airway structure and levels of TGF??1 and VEGF were significantly improved in the BMSC?treated group. Immunofluorescence observations indicated that BMSCs were able to differentiate into cells expressing vWF and VEGF, which are markers of vascular tissues. The present study demonstrated that intravenous injection of BMSCs significantly improved lung damage in a neonatal mouse model of BPD at 14 days following hyperoxia?induced injury. This provides novel information which may be used to guide further investigation into the use of stem cells in BPD.
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A validated high performance liquid chromatograph-photodiode array method for simultaneous determination of 10 bioactive components in compound hongdoushan capsule.
Pharmacogn Mag
PUBLISHED: 02-07-2014
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The compound Hongdoushan capsule (CHC) is widely known as compound herbal preparation and is often used to treat ovarian cancer and breast cancer, and to enhance the body immunity, etc., in clinical practice.
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Preparation and mechanical property of a novel 3D porous magnesium scaffold for bone tissue engineering.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 02-05-2014
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Porous magnesium has been recently recognized as a biodegradable metal for bone substitute applications. A novel porous Mg scaffold with three-dimensional (3D) interconnected pores and with a porosity of 33-54% was produced by the fiber deposition hot pressing (FDHP) technology. The microstructure and morphologies of the porous Mg scaffold were characterized by scanning electron microscopy (SEM), and the effects of porosities on the microstructure and mechanical properties of the porous Mg were investigated. Experimental results indicate that the measured Young's modulus and compressive strength of the Mg scaffold are ranged in 0.10-0.37 GPa, and 11.1-30.3 MPa, respectively, which are fairly comparable to those of cancellous bone. Such a porous Mg scaffold having a 3D interconnected network structure has the potential to be used in bone tissue engineering.
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Pinocembrin improves cognition and protects the neurovascular unit in Alzheimer related deficits.
Neurobiol. Aging
PUBLISHED: 01-29-2014
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Amyloid-? (A?) peptides accumulate in the brain and initiate a cascade of pathologic events in Alzheimer's disease. The receptor for advanced glycation end products (RAGE) has been implicated to mediate A?-induced perturbations in the neurovascular unit (NVU). We demonstrated that pinocembrin exhibits neuroprotection through inhibition of the A? and/or RAGE pathway, but the therapeutic role and mechanism involved are not ascertained. Here, we report that a 3-month treatment with pinocembrin prevents the cognition decline in APP/PS1 transgenic mice without altering A? burden and oxidative stress. Instead, pinocembrin is effective in conferring neurovascular protection through maintenance of neuropil ultrastructure, reduction of glial activation and levels of inflammatory mediators, preservation of microvascular function, improving the cholinergic system by conserving the ERK-CREB-BDNF pathway, and modulation of RAGE-mediated transduction. Furthermore, in an in vitro model, pinocembrin provides the NVU protection against fibrillar A?????, accompanied by regulation of neurovascular RAGE pathways. Our findings indicate that pinocembrin improves cognition, at least in part, attributable to the NVU protection, and highlights pinocembrin as a potential therapeutic strategy for the prevention and/or treatment of Alzheimer's disease.
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Taurine promotes human mesenchymal stem cells to differentiate into osteoblast through the ERK pathway.
Amino Acids
PUBLISHED: 01-28-2014
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Taurine has been reported to influence bone metabolism, but the role of taurine on osteogenic differentiation of human mesenchymal stem cells (hMSCs) remains unclear. In the present study, we investigated the effect of taurine on osteogenic differentiation of hMSCs. The results showed that taurine increased the alkaline phosphatase (ALP) activity and mineralized nodules in hMSCs induced by osteogenic induced medium. Meanwhile, RT-PCR analysis showed that taurine up-regulated the mRNA expression of ALP, osteopontin, Runt-related transcription factor 2 (Runx2) and Osterix in a dose-dependent manner. Furthermore, taurine induced activation of extracellular signal regulated kinase (ERK) and pretreatment with the ERK inhibitor U0126 abolished the taurine-induced osteogenesis of hMSCs. Taken together, our study reveals that taurine promotes the osteogenesis of hMSCs by activating the ERK pathway.
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Atmospheric and room temperature plasma (ARTP) as a new powerful mutagenesis tool.
Appl. Microbiol. Biotechnol.
PUBLISHED: 01-21-2014
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Developing rapid and diverse microbial mutation tool is of importance to strain modification. In this review, a new mutagenesis method for microbial mutation breeding using the radio-frequency atmospheric-pressure glow discharge (RF APGD) plasma jets is summarized. Based on the experimental study, the helium RF APGD plasma jet has been found to be able to change the DNA sequences significantly, indicating that the RF APGD plasma jet would be a powerful tool for the microbial mutagenesis with its outstanding features, such as the low and controllable gas temperatures, abundant chemically reactive species, rapid mutation, high operation flexibility, etc. Then, with the RF APGD plasma generator as the core component, a mutation machine named as atmospheric and room temperature plasma (ARTP) mutation system has been developed and successfully employed for the mutation breeding of more than 40 kinds of microorganisms including bacteria, fungi, and microalgae. Finally, the prospect of the ARTP mutagenesis is discussed.
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Re-evaluation of PRRT2 mutations in paroxysmal disorders.
J. Neurol.
PUBLISHED: 01-14-2014
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Mutations in PRRT2 have recently been identified as the major cause of autosomal dominant benign familial infantile epilepsy (BFIE), infantile convulsions with choreoathetosis syndrome (ICCA), and paroxysmal kinesigenic dyskinesia (PKD). Other paroxysmal disorders like febrile seizures, migraine, paroxysmal exercise-induced dyskinesia, and paroxysmal non-kinesigenic dyskinesia have also been shown to be associated with this gene. We re-evaluated PRRT2 mutations and genetic-clinical correlations in additional cases with PKD/ICCA and other paroxysmal disorders. Two novel mutations in PRRT2 were revealed in PKD/ICCA cases, while no mutations were detected in other diseases, which suggests BFIE and PKD are still core phenotypes of PRRT2-related spectrum disorders.
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Screening of Duchenne muscular dystrophy (DMD) mutations and investigating its mutational mechanism in Chinese patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Duchenne muscular dystrophy (DMD) is a common X-linked recessive disease of muscle degeneration and death. In order to provide accurate and reliable genetic counseling and prenatal diagnosis, we screened DMD mutations in a cohort of 119 Chinese patients using multiplex ligation-dependent probe amplification (MLPA) and denaturing high performance liquid chromatography (DHPLC) followed by Sanger sequencing. In these unrelated DMD patients, we identified 11 patients with DMD small mutations (9.2%) and 81 patients with DMD deletions/duplications (del/dup) (68.1%), of which 64 (79.0%) were deletions, 16 (19.8%) were duplications, and one (1.2%) was both deletion and duplication. Furthermore, we analyzed the frequency of DMD breakpoint in the 64 deletion cases by calculating exon-deletion events of certain exon interval that revealed a novel mutation hotspot boundary. To explore why DMD rearrangement breakpoints were predisposed to specific regions (hotspot), we precisely characterized junction sequences of breakpoints at the nucleotide level in 21 patients with exon deleted/duplicated in DMD with a high-resolution SNP microarray assay. There were no exactly recurrent breakpoints and there was also no significant difference between single-exon del/dup and multiple-exon del/dup cases. The data from the current study provided a comprehensive strategy to detect DMD mutations for clinical practice, and identified two deletion hotspots at exon 43-55 and exon 10-23 by calculating exon-deletion events of certain exon interval. Furthermore, this is the first study to characterize DMD breakpoint at the nucleotide level in a Chinese population. Our observations provide better understanding of the mechanism for DMD gene rearrangements.
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Changes in corticomotor excitability and intracortical inhibition of the primary motor cortex forearm area induced by anodal tDCS.
PLoS ONE
PUBLISHED: 01-01-2014
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Previous studies have investigated how tDCS over the primary motor cortex modulates excitability in the intrinsic hand muscles. Here, we tested if tDCS changes corticomotor excitability and/or cortical inhibition when measured in the extensor carpi radialis (ECR) and if these aftereffects can be successfully assessed during controlled muscle contraction.
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TERT promoter mutations lead to high transcriptional activity under hypoxia and temozolomide treatment and predict poor prognosis in gliomas.
PLoS ONE
PUBLISHED: 01-01-2014
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This study explored the effects of telomerase reverse transcriptase (TERT) promoter mutations on transcriptional activity of the TERT gene under hypoxic and temozolomide (TMZ) treatment conditions, and investigated the status and prognostic value of these mutations in gliomas.
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Preparation and characterizations of BGCC/Ca-P coating on pure magnesium for biomedical applications.
ACS Appl Mater Interfaces
PUBLISHED: 12-10-2013
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Magnesium has been recently recognized as a biodegradable metal for bone substitute applications. In order to improve the biocompatibility and osteointegration of pure Mg, two kinds of coatings, i.e., the Ca-P coating and bioglass ceramic cement (BGCC)/Ca-P coating were prepared on the pure Mg ribbons in the present work. The Ca-P coating was obtained by aqueous solution method. Subsequently, Ca-P coated Mg was immersed into the BGCC slurry, which was prepared by the mix of the SiO2-CaO-P2O5 bioglass ceramic (BGC) powders and the phosphate liquid with a liquid-to-solid ratio (L/S) of 1.6, to obtain BGCC/Ca-P coating by a dipping-pulling method. The microstructure, morphologies and composition of these coatings have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS). The effects of these coatings on the mineralization activity of pure Mg have been investigated. The results indicated that both the Ca-P coating and BGCC/Ca-P coating could promote the nucleation of osteoconductive minerals, i.e. bone-like apatite, and the HA layer formed on the surface of the BGCC/Ca-P coating is obviously denser, thicker and stabler than that formed on the Ca-P coating after immersion in SBF solution for 15 days. The potentiodynamic polarisation test indicated that the corrosion current density of the BGCC/Ca-P coated Mg is obviously lower than that of Ca-P coating and ten times lower than that of uncoated Mg. These results demonstrated that the BGCC/Ca-P coating can increase significantly the corrosion resistant property of Mg, and introduce a high biocompatibility of the bone-Mg substrate interface. In summary, the newly developed BGCC/Ca-P coated Mg has a good potential for biomedical applications.
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Genomic screening for targets regulated by berberine in breast cancer cells.
Asian Pac. J. Cancer Prev.
PUBLISHED: 12-03-2013
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Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.
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Polypyrrole-Enveloped Pd and Fe3O4 Nanoparticle Binary Hollow and Bowl-Like Superstructures as Recyclable Catalysts for Industrial Wastewater Treatment.
ACS Appl Mater Interfaces
PUBLISHED: 11-27-2013
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Metal and metal-oxide nanoparticles (NPs) are promising catalysts for dye degradation in wastewater treatment despite the challenges of NP recovery and recycling. In this study, water-dispersible NP superstructures with spherical morphology were constructed from hydrophobic Pd and Fe3O4 NPs by virtue of the oil droplets in an oil-in-water microemulsion as templates. Control of the evaporation rate of organic solvents in the oil droplets produces solid, hollow, and bowl-like superstructures. The component Fe3O4 and in particular Pd NPs can catalyze H2O2 degradation to create hydroxyl radicals and therewith degrade various dyes, and the magnetic Fe3O4 NPs also permit recycling of the superstructures with a magnet. Because the hollow and bowl-like superstructures increase the contact area of the NPs with their surroundings in comparison to solid superstructures, the catalytic activity is greatly enhanced. To improve the structural stability, the superstructures were further enveloped with a thin polypyrrole (PPy) shell, which does not weaken the catalytic activity. Because the current method is facile and feasible to create recyclable catalysts, it will promote the practicability of NP catalysts in treating industrial polluted water.
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Intramolecular Dehydrative Coupling of Tertiary Amines and Ketones Promoted by KO-t-Bu/DMF: A New Synthesis of Indole Derivatives.
Org. Lett.
PUBLISHED: 11-20-2013
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A new synthesis of indole derivatives has been achieved through intramolecular dehydrative coupling of tertiary amines and ketones promoted by KO-t-Bu/DMF. The reaction probably proceeds via an ?-amino alkyl radical pathway.
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Evaluation of the antibacterial activity of patchouli oil.
Iran J Pharm Res
PUBLISHED: 11-20-2013
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In the present study, the antimicrobial tests of patchouli oil were studied by using molecular docking technology and antimicrobial test in vitro. Five biological macromolecule enzymes, required by the bacteria in the process of biosynthesis were selected as target molecules. Five antibiotics benzylpenicillin, sulfadiazine, trimethoprim, rifampicin and ciprofloxacin, which are generally acknowledged as antibacterial drugs, were selected as reference compounds. The 3 three-dimensional (3D) structures of the 5 reference compounds and 26 compounds from patchouli oil were established by using surflex-dock software (8.1). And the 3D structures of five biological macromolecule enzymes derived from Protein Data Bank (PDB). Molecular docking was carried out between the 31 chemical compounds (ligands) and the 5 enzymes (receptors) by using surflex-dock function. Furthermore, the antibacterial effects of 31 chemical compounds were investigated by the scoring function after molecular docking was completed. By comparing the scoring result of 26 compounds in patchouli oil with 5 compared components, we inferred antibacterial activity in about 26 compounds in patchouli oil. On the other hand, six frequently-used pathogenic bacteria were selected for antimicrobial test in vitro, patchouli oil and its two major compounds: (-)-patchouli alcohol and pogostone, which their contents exceeded 60% in patchouli oil samples, were selected antibacterial agents. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were also determined. Molecular docking technology and antimicrobial test in vitro proved that patchouli oil had strong antimicrobial effects. Particularly, pogostone and (-)-patchouli alcohol have potent antimicrobial activity.
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Calculations on tunneling in the reactions of noradamantyl carbenes.
J. Am. Chem. Soc.
PUBLISHED: 11-11-2013
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Noradamantylchlorocarbene has been found experimentally to undergo ring expansion to 2-chloroadamantene at cryogenic temperatures. The rate constant, calculated with inclusion of small-curvature tunneling, is within a factor of 2 of the rate constant measured at 9 K in a nitrogen matrix. Our calculations predict that noradamantylfluorocarbene will not be found to rearrange under these conditions. The rate constant for carbon tunneling in the ring expansion of noradamantylmethylcarbene (1d) to 2-methyladamantene at T ? 10 K is calculated to be lower by more than 8 orders of magnitude than the rate constant for formation of 3-vinylnoradamantane from 1d by hydrogen migration.
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Preliminary antibacterial evaluation of the chemical compositions in Herba pogostemonis oil.
Pak J Pharm Sci
PUBLISHED: 11-06-2013
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In the present study, the antibacterial tests of herba pogostemonis oil were studied by using molecular- docking technology and antibacterial test in vitro. The 3 three-dimensional (3D) structures of the 5 compared compositions and 26 compositions from herba pogostemonis oil were established by using surflex-dock software (8.1). Molecular-docking was carried out between the 31 chemical compositions (ligands) and the 5 enzymes (receptors) by using surflex-dock function. By comparing the scoring result of 26 compositions in herba pogostemonis oil with 5 compared components, we can infer antibacterial activity about 26 compositions in herba pogostemonis oil. On the other hand, six frequently-used pathogenic bacteria were selected for antimicrobial test in vitro, herba pogostemonis oil and its two major compositions: (-)-herba pogostemonis alcohol and pogostone, which their contents exceeded 60% in herba pogostemonis oil samples, were selected antibacterial agents. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were also determined. Molecular-docking technology and antimicrobial test in vitro all were proved that herba pogostemonis oil had strong antibacterial effects. Particularly, pogostone and (-)-herba pogostemonis alcohol have potent antimicrobial activity.
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Modulation of Lipogenesis and Glucose Consumption in HepG2 Cells and C2C12 Myotubes by Sophoricoside.
Molecules
PUBLISHED: 11-04-2013
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Sophoricoside, an isoflavone glycoside isolated from Sophora japonica (Leguminosae), has been widely reported as an immunomodulator. In this study, the effects of sophoricoside on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were investigated. Treatment with sophoricoside at concentrations of 1-10 ?M inhibited lipid accumulation in HepG2 cells in a dose-dependent manner. At the same concentration range, no effect on cell viability was observed in the MTT assay. Inhibition of lipogenesis was associated with the downregulation of SREBP-1a, SREBP-1c, SREBP-2 and their downstream target genes (FAS, ACC, HMGR) as revealed by realtime quantitative PCR. The lipid-lowering effect was mediated via the phosphorylation of AMPK. Further investigation of the activities of this isoflavone showed that sophoricoside has the capability to increase glucose uptake by C2C12 myotubes. It also effectively inhibited the activities of ?-glucosidase and ?-amylase in vitro and remarkably lowered postprandial hyperglycaemia in starch-loaded C57BL6/J mice. These results suggest that sophoricoside is an effective regulator of lipogenesis and glucose consumption and may find utility in the treatment of obesity and type 2 diabetes.
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Efficient cyclization of tertiary amines and alkenes promoted by KOt-Bu-DMF.
Chem. Commun. (Camb.)
PUBLISHED: 10-18-2013
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Nitrogen heterocycles could be prepared in good yields via intramolecular cyclization of tertiary amines and alkenes promoted by KOt-Bu-DMF.
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Enhanced supercapacitor performance of Mn3O4 nanocrystals by doping transition-metal ions.
ACS Appl Mater Interfaces
PUBLISHED: 09-23-2013
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Pristine and transition-metal-doped Mn3O4 nanocrystals shaped in octahedrons have been synthesized by hydrothermal reduction of potassium permanganate and characterized by SEM/TEM, X-ray diffraction, X-ray photoelectron spectroscopy, and electrochemical experiments. The results reveal that a multistep reduction process is taking place, and the introduction of doping ions causes a direct synthesis of single-phase Mn3O4 nanocrystals. To assess the properties of Mn3O4 nanocrystals for their use in supercapacitors, cyclic voltammetry and galvanostatic charging-discharging measurements are performed. The phase stability during cycling and charge-transfer behavior are greatly improved by doping with transition metal, and Cr-doped Mn3O4 nanocrystals exhibit a maximum specific capacitance of 272 F g(-1) at a current density of 0.5 A g(-1). These doped Mn3O4 nanocrystals could be a promising candidate material for high-capacity, low-cost, and environmentally friendly electrodes for supercapacitors. In addition, these results have verified the ability of doping to improve capacitive performances of spinel-structured transition-metal oxides.
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Ecotoxicity assessment of artificial groundwater recharge with reclaimed water: a pilot-scale study.
Bull Environ Contam Toxicol
PUBLISHED: 09-12-2013
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A demonstration of artificial groundwater recharge with tertiary effluent was evaluated using a set of bioassays (acute toxicity to Daphnia, genotoxicity, estrogenic and antiestrogenic toxicity). Around 95 % genotoxicity and 53 % antiestrogenicity were removed from the feed water by ozonation, whereas significant reduction of acute toxicity to Daphnia magna was achieved during a 3 days vadose soil treatment. The toxicity was further removed to the same level as the local groundwater during a 20 days aquifer soil treatment. The pilot study has shown that ozonation and soil treatments can improve the quality of municipal wastewater treatment plant effluents for possible groundwater recharge purposes.
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[Gestational weight gain and its relationship with the birthweight of offspring].
Zhonghua Fu Chan Ke Za Zhi
PUBLISHED: 09-11-2013
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To explore the appropriate weight gain during pregnancy and its relationship with the birthweight of offspring.
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Prognostic characteristics of gastrointestinal tract NK/T-cell lymphoma: an analysis of 47 patients in China.
J. Clin. Gastroenterol.
PUBLISHED: 08-17-2013
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The gastrointestinal tract is the most common primary site of extranodal lymphomas, whereas gastrointestinal natural killer/T-cell (GINKT) lymphomas are relatively rare. To date, neither the prognostic characteristics nor the clinical features or optimal therapeutic approach for GINKT has yet been defined.
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The effect of PS-341 on pulmonary vascular remodeling in high blood flow-induced pulmonary hypertension.
Int. J. Mol. Med.
PUBLISHED: 07-27-2013
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The aim of the present study was to investigate the effects of PS-341 on vascular remodeling in an experimental rat model of high blood flow-induced pulmonary arterial hypertension (PAH), as well as to elucidate its mechanisms of action. We established the PAH model by a surgical method that implanted a left-to-right shunt. Three days post-surgery, the animals were randomly assigned to 3 groups (n=15 in each group): sham-operated (control), shunt (model) and PS-341 (treated) groups. Eight weeks post-surgery, hemodynamic parameters were significantly improved in the PS-341 group compared with the shunt group (P<0.05). Immunohistochemical analysis indicated that the expression levels of ubiquitin and nuclear factor-?B (NF-?B) p65 were significantly higher in the shunt group compared with the sham-operated group (P<0.05). Semi-quantitative western blot analysis further confirmed that the levels of ubiquitin and NF-?B p65 were decreased, while those of I?B-? (an inhibitor of NF-?B) were significantly increased in the PS-341 group compared with the shunt group (P<0.05). In conclusion, PS-341 attenuates high blood flow-induced pulmonary artery remodeling in rats via inhibition of the NF-?B pathway.
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[Study on multi-level fractal features extraction method of breast mass].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-18-2013
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Breast mass is womens common disease, and it seriously affects the health of women. Accurate detection and location of the mass will greatly improve the precision of the diagnosis of the breast disease. Studies have shown that the organizational structure and surface roughness of the mass constitute the texture features of mass and it is an important basis for distinguishing the mass. In this paper, a multi-level fractal features extraction method is proposed, and, moreover, the fractal feature vector of the suspicious lesions has been established, thus realizing the feature extraction and analysis of the mammary gland. Finally, the result of classification with the support vector machine (SVM) was given. 110 mammograms are extracted and classified with an accuracy of 90%. The results showed that the multi-level fractal features extraction and classification methods proposed in this paper could improve the accuracy of mass detection and could be effective for the early diagnosis of the disease.
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[Intrahepatic cholestasis of pregnancy and fetal injury].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 07-06-2013
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Intrahepatic cholestasis of pregnancy (ICP) is an unique complication in pregnancy, which usually manifests in the second or third trimester, and mainly harms the fetus. Its pathogenesis is not yet clear, and placental pathological changes are insufficient to explain the clinical phenomenon.Recent studies had shown that the important cause of perinatal deaths may be the damage to the placental structure and function caused by the high bile acid level. In addition, the change of placental structure and function, umbilical cord factors, and endocrine changes can also cause the fetal development and intrauterine hypoxia. In recent years related researches focus on the toxic effect of bile acid on fetus heart, lungs, brain, liver, and other important organs, the placental vascular pathology, hemodynamic changes, umbilical cord blood vessel factors and the endocrine changes.
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Effect of Danggui Buxue Tang on immune-mediated aplastic anemia bone marrow proliferation mice.
Phytomedicine
PUBLISHED: 06-23-2013
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To investigate the pharmacological effects of Danggui Buxue Tang (DBT) on immune-mediated aplasia anemia mice. The model of immune-mediated aplasia anemia mice was induced by means of (60)Co ?-ray irradiation and mixed cells of thymus and lymphnode of DBA/2 mice infusion through tail vein, the parameters tested indices were as following: blood picture, bone marrow nucleated cell count (BMNC), murine colony-forming unit-megakaryocytes (CFU-GM) of bone marrow cells, murine colony-forming unit-erthroid (CFU-E) and burst forming unit-erythroid (BFU-E). The results showed that DBT could not only withstand significantly decreation of blood cells by immune-mediated, but also stimulate on the growth of bone marrow colony cell and increase the weight of hemopoietic progenitor of bone marrow. Therefore, DBT had an obvious treat effect on immune-mediated aplasia anemia models mice.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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

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