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Find video protocols related to scientific articles indexed in Pubmed.
Complete Nucleotide Sequence of cfr-carrying IncX4 Plasmid, pSD11, from Escherichia coli.
Antimicrob. Agents Chemother.
PUBLISHED: 11-19-2014
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We report a complete nucleotide sequence of a plasmid carrying the multi-resistance gene cfr. This plasmid was isolated from an Escherichia coli strain of swine origin in 2011. This 37,672-bp plasmid, pSD11, had an IncX4 backbone similar to that of the IncX4 plasmids obtained from the USA and Australia, in which the cfr gene was flanked by two copies of IS26, and a truncated Tn1331 inserted.
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Histological and developmental study of prehierarchical follicles in geese.
Folia Biol. (Krakow)
PUBLISHED: 11-19-2014
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The development of the follicular wall and apoptosis of corresponding cells are dependent upon the stage of follicle growth and levels of endogenous hormones. However, the development and apoptosis of prehierarchical follicles in geese is insufficiently known. In order to obtain an understanding about the microstructure, development and apoptosis of prehierarchical follicles in geese, firstly, a histological method was used to investigate the morphological structure of prehierarchical follicles. Results showed that the thickness of granulosa cell layers of the follicular wall increased first, then decreased to the lowest when follicles grew to 9-10 mm in diameter, and the theca layers also thinned to the lowest thickness at the same stage. Moreover, the expression of follicle-stimulating hormone receptor (FSHR) mRNA and the enzyme activity of caspase-3 were analyzed and the results showed that the expression of FSHR was highest when follicles grew to 8-9 mm in diameter (p < 0.05); the enzyme activity of caspae-3 was the highest when follicles grew to 6-8 mm in diameter (p < 0.05). These collective findings suggested that follicles 6-10 mm in diameter were especially significant, and perhaps represent a turning point from growing follicles to dominant follicles to be selected into a hierarchical sequence or to other follicles to be degenerated during prehierarchical follicle development.
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Venous cannula performance assessment in a realistic caval tree model.
Interact Cardiovasc Thorac Surg
PUBLISHED: 11-05-2014
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A new caval tree system was designed for realistic in vitro simulation. The objective of our study was to assess cannula performance for virtually wall-less versus standard percutaneous thin-walled venous cannulas in a setting of venous collapse in case of negative pressure.
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[Effect of dangua recipe on glycolipid metabolism and VCAM-1 and its mRNA expression level in Apo E(-/-) mice with diabetes mellitus].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 10-23-2014
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To study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy.
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[Effect of advanced glycosylation end products on oxidative stress and MCP-1 in human renal mesangial cells].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 10-22-2014
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To investigate the effects of advanced glycosylation end products(AGEs)modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs).
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Oxidized high-density lipoprotein impairs endothelial progenitor cells function by activation of CD36-MAPK-TSP-1 pathways.
Antioxid. Redox Signal.
PUBLISHED: 10-15-2014
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Aims: High density lipoprotein (HDL) levels inversely correlate with cardiovascular events due to the protective effects on vascular wall and stem cells, which is susceptible to oxidative modifications and then leads to potential pro-atherosclerotic effects. We proposed that oxidized high density lipoprotein (ox-HDL) might lead to endothelial progenitor cells (EPCs) dysfunction and investigated underlying mechanisms. Results: ox-HDL was shown to increase apoptosis and intracellular ROS levels, but reduce migration, angiogenesis and cholesterol efflux of EPCs in a dose dependent manner. p38 mitogen-activated protein kinase (MAPK) and NF-?B were activated after ox-HDL stimulation, which also upregulated thrombospondin-1 expression without affecting vascular endothelial growth factor. Effects caused by ox-HDL could be significantly attenuated by pretreatment with shRNA-mediated CD36 knockdown or probucol. Data of in vivo experiments and the inversely correlation of ox-HDL and circulating EPC numbers among patients with coronary artery diseases or CAD and type 2 diabetes also supported it. Meanwhile HDL separated from such patients could significantly increase cultured EPC's caspase 3 activity, furthermore supporting our proposal. Innovation: This is the most complete study to date of how ox-HDL would impair EPCs function, which was involved with activation of CD36-p38 MAPK-TSP-1 pathways and proved by not only the inverse relationship between ox-HDL and circulating EPCs in clinic, but also pro-apoptotic effects of HDL separated from patients' serum. Conclusion: Activation of CD36-p38 MAPK-TSP-1 pathways contributes to the pathological effects of ox-HDL on EPCs' dysfunction, which might be one of potential etiological factors responsible for the disturbed neovascularization in chronic ischemic disease.
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Gene expression patterns, and protein metabolic and histological analyses for muscle development in Peking duck.
Poult. Sci.
PUBLISHED: 10-13-2014
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In this study, we aimed to use duck breast muscle and leg muscle, the 2 main productive muscle organs, as a model to elucidate the molecular mechanism controlling how the 2 muscles have different deposition capabilities, and to analyze the mechanisms facilitating duck muscle development posthatching. Peking duck breast muscle and leg muscle were collected 3, 7, and 16 wk posthatching. The morphology of the myofibers was observed by paraffin sectioning the muscles. The expression of genes involved in protein metabolism [mammalian target of rapamycin (mTOR), RPS6-p70-protein kinase (S6K), forkhead box O1 (FoxO1), muscle RING finger 1 (MuRF1), and atrogin-1 (MAFbx)] was detected using real-time quantitative PCR and Western blot assays, and the results indicated that breast muscle had a stronger capacity for both protein synthesis and protein degradation compared with leg muscle. Satellite cell frequency declined during muscle development in both tissues, and the expression of Pax3/7, satellite cell marker genes, was not significantly different between breast muscle and leg muscle. No notable apoptosis was observed in either tissue. The results of this study suggest that protein metabolism signaling is the main reason promoting duck skeletal muscle mass gain.
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Molecular cloning and expression pattern of duck Six1 and its preliminary functional analysis in myoblasts transfected with eukaryotic expression vector.
Indian J. Biochem. Biophys.
PUBLISHED: 10-10-2014
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Skeletal muscle development is regulated by Six1, an important myogenic transcription factor. However, the functional analysis of duck Six1 has not been reported. Here, we cloned the coding domain sequence (CDS) region of the duck Six1 gene using RT-PCR and RACE methods. Bioinformatics analysis revealed that duck Six1 CDS region comprised of 849 bp and encoded 282 amino acids and had a high degree of homology with other species, suggesting that the functions of duck Six1 gene are conserved among other animals. Real-time PCR used to determine the mRNA expression profiles of duck Six1 in different tissues and different developmental stages showed that Six1 was highly expressed in skeletal muscle and the embryonic stage. Furthermore, the eukaryotic expression vector pEGFP-duSix1 was constructed and transfected into the duck myoblasts; the MTT assay revealed an obvious increase of cell proliferation after transfection. The expression profiles of Six1, Myf5 and MyoD showed that their expression levels were significantly increased. These results together suggested that pEGFP-duSix1 vector was constructed successfully and overexpression of duck Six1 in the myoblasts could promote cell proliferation activity and significant up-regulate expression of Myf5 and MyoD.
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Ultraeffective ZnS Nanocrystals Sorbent for Mercury(II) Removal Based on Size-Dependent Cation Exchange.
ACS Appl Mater Interfaces
PUBLISHED: 10-09-2014
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We report a novel nanocrystals (NCs) sorbent, which shows an extraordinary adsorption capacity to aqueous Hg(2+) based on cation exchange and allows for the utmost removal of mercury from water. The NCs sorbent was synthesized by direct coating ZnS NCs on the surface of the ?-Al2O3 nanoparticles. The as-prepared ZnS NCs sorbent can efficiently remove over 99.9% Hg(2+) in 1 min, and lower the Hg(2+) concentration from 297.5 mg/L (ppm) to below 1.0 ?g/L (ppb) within 5 min. The saturated adsorption capacity of ZnS NCs for Hg(2+) is about 2000 mg/g, which is close to the theoretic saturated adsorption capacity. The mechanism of Hg(2+) removal by ZnS NCs sorbent, the influences of pH value and other cations on Hg(2+) removal were investigated, respectively. Meanwhile, it is found the size-dependent cation exchange plays a critical role in the removal of Hg(2+) by ZnS NCs. Small size ZnS NCs shows better performance than the big size ZnS NCs in the adsorption capacity and adsorption rate for Hg(2+). Furthermore, the mercury adsorbed by the ZnS NCs sorbent is readily recycled by extraction with aqueous sodium sulfide.
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From Bad to Worse: Anemia on Admission and Hospital-Acquired Anemia.
J Patient Saf
PUBLISHED: 10-08-2014
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Anemia at hospitalization is often treated as an accompaniment to an underlying illness, without active investigation, despite its association with morbidity. Development of hospital-acquired anemia (HAA) has also been associated with increased risk for poor outcomes. Together, they may further heighten morbidity risk from bad to worse.
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Simultaneous enrichment and separation of flavonoids from Herba Epimedii by macroporous resins coupled with preparative chromatographic method.
Nat. Prod. Res.
PUBLISHED: 10-03-2014
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An efficient, feasible enrichment and separation method of epimedins A, B, C and icariin from Herba Epimedii was developed by the combination of microwave-assisted extraction, macroporous resins and preparative HPLC. WDX-5 macroporous resin shows better recoveries at 96.2%, 97.0%, 98.2% and 97.1% for epimedins A, B, C and icariin than other macroporous resins used in the experiments. As a result, epimedins A (5.1 mg), B (15.3 mg), C (7.6 mg) and icariin (14.3 mg) were obtained from 6.0 g crude Herba Epimedii with the recoveries at 70.8%, 68.9%, 66.7% and 95.3%, respectively. The method developed in this study may provide scientific references for the enrichment and separation of flavonoids from Herba Epimedii.
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Quantitative metabolomic profiling using dansylation isotope labeling and liquid chromatography mass spectrometry.
Methods Mol. Biol.
PUBLISHED: 10-02-2014
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Differential chemical isotopic labeling (CIL) LC-MS has been used for quantifying a targeted metabolite in biological samples with high precision and accuracy. Herein we describe a high-performance CIL LC-MS method for generating quantitative and comprehensive profiles of the metabolome for metabolomics applications. After mixing two comparative samples separately labeled by light or heavy isotopic tags through chemical reactions, the peak intensity ratio of the labeled analyte pair can provide relative or absolute quantitative information on the metabolites. We describe the use of (12)C2- and (13)C2-dansyl chloride (DnsCl) as the isotope reagents to profile the metabolites containing amine and phenolic hydroxyl functional groups by LC-MS. This method can be used to compare the relative concentration changes of hundreds or thousands of amine- and phenol-containing metabolites among many comparative samples and generate absolute concentration information on metabolites for which the standards are available. Combined with statistical analysis and metabolite identification tools, this method can be used to identify key metabolites involved in differentiating comparative samples such as disease cases vs. healthy controls.
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Controlling the Ring Curvature, Solution Assembly, and Reactivity of Gigantic Molybdenum Blue Wheels.
J. Am. Chem. Soc.
PUBLISHED: 09-29-2014
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We describe the synthesis, structure, self-assembly, solution chemistry, and mass spectrometry of two new gigantic decameric molybdenum blue wheels, {Mo200Ce12} (1) and {Mo100Ce6} (2), by building block rearrangement of the tetradecameric {Mo154} framework archetype and control of the architecture's curvature in solution from the addition of Ce(III). The assembly of 1 and 2 could be directed accordingly by adjusting the ionic strength and acidity of the reaction mixture. Alternatively, the dimeric cluster {Mo200Ce12} could be transformed directly to the monomeric species {Mo100Ce6} upon addition of a potassium salt. ESI-ion mobility mass spectra were successfully obtained for both {Mo200Ce12} and {Mo100Ce6}, which is the first report in molybdenum blue chemistry thereby confirming that the gigantic clusters are stable in solution and that ion mobility measurements can be used to characterize nanoscale inorganic molecules.
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Surface-step-induced oscillatory oxide growth.
Phys. Rev. Lett.
PUBLISHED: 09-25-2014
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We report in situ atomic-resolution transmission electron microscopy observations of the oxidation of stepped Cu surfaces. We find that the presence of surface steps both inhibits oxide film growth and leads to the oxide decomposition, thereby resulting in oscillatory oxide film growth. Using atomistic simulations, we show that the oscillatory oxide film growth is induced by oxygen adsorption on the lower terrace along the step edge, which destabilizes the oxide film formed on the upper terrace.
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Spectral CT Modeling and Reconstruction with Hybrid Detectors in Dynamic-threshold-based Counting and Integrating Modes.
IEEE Trans Med Imaging
PUBLISHED: 09-25-2014
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Spectral CT with photon counting detectors can significantly improve CT performance by reducing image noise and dose, increasing contrast resolution and material specificity, as well as enabling functional and molecular imaging with existing and emerging probes. However, the current photon counting detector architecture is difficult to balance the number of energy bins and the statistical noise in each energy bin. Moreover, the hardware support for multi-energy bins demands a complex circuit which is expensive. In this paper, we promote a new scheme known as hybrid detectors that combine the dynamic-threshold-based counting and integrating modes. In this scheme, an energy threshold can be dynamically changed during a spectral CT scan, which can be considered as compressive sensing along the spectral dimension. By doing so, the number of energy bins can be retrospectively specified, even in a spatially varying fashion. To establish the feasibility and merits of such hybrid detectors, we develop a tensor-based PRISM algorithm to reconstruct a spectral CT image from dynamic dual-energy data, and perform experiments with simulated and real data, producing very promising results.
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Short and efficient synthesis of fluorinated ?-lactams.
Org. Biomol. Chem.
PUBLISHED: 09-24-2014
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The diastereoselective synthesis of fluorinated ?-lactams has been achieved through an efficient five step process. The route can tolerate a range of functionalities, and provides a quick route for the generation of new fluorinated medicinal building blocks.
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Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm.
Arch. Pharm. Res.
PUBLISHED: 09-23-2014
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Baicalin, a flavonoid, has a wide range of pharmacological properties, including immunomodulation. The objective of this study was to investigate the effect of baicalin on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in a colitis model. The rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baicalin (10 ml/kg, each) or mesalazine (positive control) was then administered orally for 7 days. Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. Our study showed that baicalin not only significantly attenuated TNBS-induced colitis by reducing the disease activity index as well as macroscopic and microscopic scores, but it also improved the weight loss and shortening of the colon. Baicalin treatment also induced a significant decrease in the levels of inflammatory mediators, including the myeloperoxidase activity, the levels of tumor necrosis factor ?, IL-1?, and Th1-related cytokines IL-12 and IFN-?. Furthermore, the beneficial effects of baicalin seem to be associated with regulation of the Th17 and Treg paradigm. We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor ?t. In contrast, there was an increase in Treg cells numbers, Treg-related cytokines transforming growth factor-? and IL-10, and forkhead box P3. Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis.
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Overexpression of MicroRNA-30b Improves Adenovirus-Mediated p53 Cancer Gene Therapy for Laryngeal Carcinoma.
Int J Mol Sci
PUBLISHED: 09-22-2014
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MicroRNAs play important roles in laryngeal carcinoma and other cancers. However, the expression of microRNAs in paracancerous tissue has been studied less. Here, using laser capture microdissection (LCM), we detected the expression of microRNAs in paracancerous tissues. Among all down-regulated microRNAs in the center area of tumor tissues, only miR-30b expression was significantly reduced in paracancerous tissues compared to surgical margins. Therefore, to further investigate the effect of miR-30b on laryngeal carcinoma, we stably overexpressed miR-30b in laryngeal carcinoma cell line HEp-2 cells. It was found that although there was no significant difference in cell viability between miR-30b overexpressed cells and control HEp-2 cells, p53 expression was obviously enhanced in miR-30b overexpressed cells. Whether miR-30b could improve the anti-tumor effect of adenovirus-p53 (Ad-p53) in laryngeal carcinoma and other cancer cell lines was also evaluated. It was found that in miR-30b overexpressed HEp-2 cells, p53-mediated tumor cell apoptosis was obviously increased both in vitro and in vivo. MDM2-p53 interaction might be involved in miR-30b-mediated anti-tumor effect. Together, results suggested that miR-30b could modulate p53 pathway and enhance p53 gene therapy-induced apoptosis in laryngeal carcinoma, which could provide a novel microRNA target in tumor therapy.
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Mining Tissue-specific Contigs from Peanut (Arachis hypogaea L.) for Promoter Cloning by Deep Transcriptome Sequencing.
Plant Cell Physiol.
PUBLISHED: 09-16-2014
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Peanut (Arachis hypogaea L.), one of the most important oil legumes in the world, is heavily damaged by white grubs. Tissue-specific promoters are needed to incorporate insect resistance genes into peanut by genetic transformation to control the subterranean pests. Transcriptome sequencing is the most effective way to analyze differential gene expression in this non-model species and contribute to promoter cloning. The transcriptomes of the roots, seeds and leaves of peanut were sequenced using Illumina technology. A simple digital expression profile was established based on number of transcripts per million clean tags (TPM) from different tissues. Subsequently, 584 root-specific candidate transcript assembly contigs (TACs) and 316 seed-specific candidate TACs were identified. Among these candidate TACs, 55.3% were root-specific and 64.6% were seed-specific by semi-quantitative RT-PCR analysis. Moreover, the consistency of semi-quantitative RT-PCR with the simple digital expression profile was correlated with the length and TPM value of TACs. The results of gene ontology showed that some root-specific TACs are involved in stress resistance and respond to auxin stimulus, whereas, seed-specific candidate TACs are involved in embryo development, lipid storage and long-chain fatty acid biosynthesis. One root-specific promoter was cloned and characterized. We developed a high-yield screening system in peanut by establishing a simple digital expression profile based on Illumina sequencing. The feasible and rapid method presented by this study can be used for other non-model crops to explore tissue-specific or spatially specific promoters.
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Immunization with advanced glycation end products modified low density lipoprotein inhibits atherosclerosis progression in diabetic apoE and LDLR null mice.
Cardiovasc Diabetol
PUBLISHED: 09-15-2014
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BackgroundDiabetes propitiates atherosclerosis through undefined molecular mechanisms. Hyperglycemia induces formation of advanced glycation end product (AGE)-modified low-density lipoprotein (LDL). Anti-AGE-LDL autoantibodies favor atherosclerosis (AS) progression in humans, while anti oxidized LDL immunization inhibits AS in hypercholesterolemic, non-diabetic mice. We here investigated if AGE-LDL immunization protects against AS in diabetic mice.MethodsAfter diabetes induction with streptozotocin and high fat diet, both low density lipoprotein receptor (LDLR)¿/¿ and apoE female mice were randomized to: AGE-LDL immunization with aluminum hydroxide (Alum) adjuvant; Alum alone; or PBS.ResultsAGE-LDL immunization: significantly reduced AS; induced specific plasma IgM and IgG antibodies; upregulated splenic Th2, Treg and IL-10 levels, without altering Th1 or Th17 cells; and increased serum high density lipoprotein(HDL) while numerically lowering HbA1c levels.ConclusionsSubcutaneous immunization with AGE-LDL significantly inhibits atherosclerosis progression in hyperlipidemic diabetic mice possibly through activation of specific humoral and cell mediated immune responses and metabolic control improvement.
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[Effect of advanced glycation end products on the function and angiogenesis of adipose tissue-derived stem cells and the protective effect of danhong injection: an experimental study].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 08-21-2014
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OBJECTIVE To investigate the effect of Nepsilon-(carboxymethyl) lysine albumin (CMLs), a primary advanced glycation end products (AGEPs) isoform in diabetic body, on the function and angiogenesis of adipose tissue-derived stem cells (ADSCs) and the protective effect of Danhong Injection (DH). METHODS Human ADSCs were cultured and separated from human subcutaneous fatty tissue using enzymatic digestion and centrifugation. The morphology was observed using optical microscope and differentiation capacities assessed. Cells were exposed to 5 different interventions respectively for 24 h, i.e., PBS, 60 1 microg/mL BSA, 60 microg/mL CML-BSA, 100 microL/mL DH, and 60 micro./mL CML-BSA +100 microL/mL DH. Their effect on the proliferation, migration, apoptosis, and secretion were observed using WST-1 assay, Transwell assay, Annexin V-FITC/PI flow meter test reagent kit, human VEGF reagent kit, ELISA reagent kit, respectively. The effect on ADSCs angiogenesis was observed by in vitro angiogenesis test.
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Recombinase Polymerase Amplification (RPA) of CaMV-35S Promoter and nos Terminator for Rapid Detection of Genetically Modified Crops.
Int J Mol Sci
PUBLISHED: 08-14-2014
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Recombinase polymerase amplification (RPA) is a novel isothermal DNA amplification and detection technology that enables the amplification of DNA within 30 min at a constant temperature of 37-42 °C by simulating in vivo DNA recombination. In this study, based on the regulatory sequence of the cauliflower mosaic virus 35S (CaMV-35S) promoter and the Agrobacterium tumefaciens nopaline synthase gene (nos) terminator, which are widely incorporated in genetically modified (GM) crops, we designed two sets of RPA primers and established a real-time RPA detection method for GM crop screening and detection. This method could reliably detect as few as 100 copies of the target molecule in a sample within 15-25 min. Furthermore, the real-time RPA detection method was successfully used to amplify and detect DNA from samples of four major GM crops (maize, rice, cotton, and soybean). With this novel amplification method, the test time was significantly shortened and the reaction process was simplified; thus, this method represents an effective approach to the rapid detection of GM crops.
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Comparative analyses between retained introns and constitutively spliced introns in Arabidopsis thaliana using random forest and support vector machine.
PLoS ONE
PUBLISHED: 08-11-2014
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One of the important modes of pre-mRNA post-transcriptional modification is alternative splicing. Alternative splicing allows creation of many distinct mature mRNA transcripts from a single gene by utilizing different splice sites. In plants like Arabidopsis thaliana, the most common type of alternative splicing is intron retention. Many studies in the past focus on positional distribution of retained introns (RIs) among different genic regions and their expression regulations, while little systematic classification of RIs from constitutively spliced introns (CSIs) has been conducted using machine learning approaches. We used random forest and support vector machine (SVM) with radial basis kernel function (RBF) to differentiate these two types of introns in Arabidopsis. By comparing coordinates of introns of all annotated mRNAs from TAIR10, we obtained our high-quality experimental data. To distinguish RIs from CSIs, We investigated the unique characteristics of RIs in comparison with CSIs and finally extracted 37 quantitative features: local and global nucleotide sequence features of introns, frequent motifs, the signal strength of splice sites, and the similarity between sequences of introns and their flanking regions. We demonstrated that our proposed feature extraction approach was more accurate in effectively classifying RIs from CSIs in comparison with other four approaches. The optimal penalty parameter C and the RBF kernel parameter [Formula: see text] in SVM were set based on particle swarm optimization algorithm (PSOSVM). Our classification performance showed F-Measure of 80.8% (random forest) and 77.4% (PSOSVM). Not only the basic sequence features and positional distribution characteristics of RIs were obtained, but also putative regulatory motifs in intron splicing were predicted based on our feature extraction approach. Clearly, our study will facilitate a better understanding of underlying mechanisms involved in intron retention.
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MicroRNA-26a/b Regulate DNA Replication Licensing, Tumorigenesis, and Prognosis by Targeting CDC6 in Lung Cancer.
Mol. Cancer Res.
PUBLISHED: 08-06-2014
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Cancer is characterized by mutations, genome rearrangements, epigenetic changes, and altered gene expression that enhance cell proliferation, invasion, and metastasis. To accommodate deregulated cellular proliferation, many DNA replication-initiation proteins are overexpressed in human cancers. However, the mechanism that represses the expression of these proteins in normal cells and the cellular changes that result in their overexpression are largely unknown. One possible mechanism is through miRNA expression differences. Here, it is demonstrated that miR26a and miR26b inhibit replication licensing and the proliferation, migration, and invasion of lung cancer cells by targeting CDC6. Importantly, miR26a/b expression is significantly decreased in human lung cancer tissue specimens compared with the paired adjacent normal tissues, and miR26a/b downregulation and the consequential upregulation of CDC6 are associated with poorer prognosis of patients with lung cancer. These results indicate that miR26a/b repress replication licensing and tumorigenesis by targeting CDC6.
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Antitumor effects of dammarane-type saponins from steamed Notoginseng.
Pharmacogn Mag
PUBLISHED: 07-24-2014
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Six dammarane-type saponins were extracted from steamed Panax notoginseng. Their chemical structures were identified spectroscopically as ginsenosides Rh1 (1), Rg1 (2), 20 (S)-Rg3 (3), 20 (R)-Rg3 (4), Rb3 (5), and Rb1 (6). Compounds (0.1-10 ?M) were tested for inhibition of tumor necrosis factor-? (TNF)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) luciferase reporter activity using a human kidney 293T cell-based assay. Ginsenoside Rb3 (5) showed the most significant activity with an IC50 of 8.2 ?M. This compound also inhibited the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) messenger Ribonucleic acid (mRNA) in a dose-dependent manner after HepG2 cells had been treated with TNF-? (10 ng/mL).
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Insights into the mechanisms of chitosan-anionic polymers-based matrix tablets for extended drug release.
Int J Pharm
PUBLISHED: 07-17-2014
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The aim of this study was to investigate drug release mechanisms from physical mixtures of chitosan-anionic polymers-based matrix tablets and to obtain a comprehensive understanding about release characteristics. Six types of anionic polymers (i.e., Eudragit(®) L100, sodium alginate, carrageenan, carboxymethylcellulose sodium, carbomer and xanthan gum) and two model drugs (i.e., theophylline and metoprolol succinate) with varied solubility were chosen. Texture analyzer, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were applied to better understand drug release mechanisms. In vitro release experiments were conducted in a pH-changing medium to simulate the physiological condition of the gastrointestinal tract. Interestingly, a common phenomenon was observed in all the CS-anionic polymers-based matrix tablets investigated here, that is, the inner layer of the swollen tablets was coated by CS-anionic polymer polyelectrolyte complexes (PEC)-based film formed by self-assembly. Formation of the in situ self-assembled film was further confirmed by texture analysis, DSC, and FTIR. It was further identified that properties of the film were influenced by the characteristics of anionic polymers and the physiological conditions of the gastrointestinal tract. Moreover, this novel structure could alter swelling and erosion-based release mechanisms of the tablets. In addition, drug release characteristics from CS-anionic polymer systems depended on the properties of anionic polymers and the drug solubility. In conclusion, our studies may broaden current views on cationic polymer-anionic polymer-based oral matrix tablets for extended release.
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Profiling of alternative polyadenylation sites in luminal B breast cancer using the SAPAS method.
Int. J. Mol. Med.
PUBLISHED: 07-09-2014
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Breast cancer (BC) is a leading cause of cancer-related mortality in females and is recognized as a molecularly heterogeneous disease. Previous studies have suggested that alternative messenger RNA (mRNA) processing, particularly alternative polyadenylation [poly(A)] (APA), can be a powerful molecular biomarker with prognostic potential. Therefore, in the present study, we profiled APA sites in the luminal B subtype of BC by sequencing APA sites (SAPAS) method, in order to assess the relation of these APA site-switching events to the recognized molecular subtypes of BC, and to discover novel candidate genes and pathways in BC. Through comprehensive analysis, the trend of APA site-switching events in the 3' untranslated regions (3'UTRs) in the luminal B subtype of BC were found to be the same as that in MCF7 cell lines. Among the genes involved in the events, a significantly greater number of genes was found with shortened 3'UTRs in the samples, which were samples of primary cancer with relatively low proliferation. These findings may provide novel information for the clinical diagnosis and prognosis on a molecular level. Several potential biomarkers with significantly differential tandem 3'UTRs and expression were found and validated. The related biological progresses and pathways involved were partly confirmed by other studies. In conclusion, this study provides new insight into the diagnosis and prognosis of BC from the APA site profile aspect.
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Anticancer effects of ?-elemene in gastric cancer cells and its potential underlying proteins: A proteomic study.
Oncol. Rep.
PUBLISHED: 07-04-2014
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Gastric cancer is a common malignancy with a poor prognosis. ?-elemene is a broad-spectrum anticancer drug extracted from the traditional Chinese medicinal herb Curcuma wenyujin. In the present study, we investigated the anticancer effects of ?-elemene in gastric cancer cells and the potential proteins involved. Human SGC7901 and MKN45 gastric cancer cells were treated with different concentrations of ?-elemene. Cell viability, clonogenic survival and apoptotic cell death were assessed. ?-elemene inhibited viability and decreased clonogenic survival of gastric cancer cells in a dose-dependent manner. Apoptosis induction contributed to the anticancer effects. We then employed a proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), to detect the proteins altered by ?-elemene. In total, 147 upregulated proteins and 86 downregulated proteins were identified in response to ?-elemene treatment in SGC7901 gastric cancer cells. Among them, expression of p21-activated protein kinase?interacting protein 1 (PAK1IP1), Bcl-2-associated transcription factor 1 (BTF) and topoisomerase 2-? (TOPII?) were validated by western blot analyses and the trends were consistent with iTRAQ results. Top pathways involved in ?-elemene treatment in SGC7901 gastric cancer cells included ribosome signaling, peroxisome proliferator-activated receptors (PPARs) signaling pathway, regulation of actin cytoskeleton, phagosome, biosynthesis and metabolism of some amino acids. Collectively, our results suggest a promising therapeutic role of ?-elemene in gastric cancer. The differentially expressed proteins provide further insight into the potential mechanisms involved in gastric cancer treatment using ?-elemene.
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Infection of Ustilaginoidea virens intercepts rice seed formation but activates grain-filling-related genes.
J Integr Plant Biol
PUBLISHED: 06-27-2014
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Rice false smut has become an increasingly serious disease in rice production worldwide. The typical feature of this disease is that the fungal pathogen Ustilaginoidea virens (Uv) specifically infects rice flower and forms false smut balls, the ustiloxins-containing ball-like fungal colony, of which the size is usually several times larger than that of a mature rice seed. However, the underlying mechanisms of Uv-rice interaction are poorly understood. Here, we applied time-course microscopic and transcriptional approaches to investigate rice responses to Uv infection. The results demonstrated that flower-opening process and expression of associated transcription factors, including ARF6 and ARF8, were inhibited in Uv-infected spikelets. The ovaries in infected spikelets were interrupted in fertilization and thus were unable to set seeds. However, a number of grain-filling-related genes, including seed storage protein genes, starch anabolism genes and endosperm-specific transcription factors (RISBZ1 and RPBF), were highly transcribed as if the ovaries were fertilized. In addition, critical defense-related genes like NPR1 and PR1 were down-regulated by Uv infection. Our data imply that Uv might hijack host nutrient reservoir by activation of grain-filling network for the need of growth and formation of false smut balls.
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Design and fabrication of memory devices based on nanoscale polyoxometalate clusters.
Nature
PUBLISHED: 06-26-2014
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Flash memory devices-that is, non-volatile computer storage media that can be electrically erased and reprogrammed-are vital for portable electronics, but the scaling down of metal-oxide-semiconductor (MOS) flash memory to sizes of below ten nanometres per data cell presents challenges. Molecules have been proposed to replace MOS flash memory, but they suffer from low electrical conductivity, high resistance, low device yield, and finite thermal stability, limiting their integration into current MOS technologies. Although great advances have been made in the pursuit of molecule-based flash memory, there are a number of significant barriers to the realization of devices using conventional MOS technologies. Here we show that core-shell polyoxometalate (POM) molecules can act as candidate storage nodes for MOS flash memory. Realistic, industry-standard device simulations validate our approach at the nanometre scale, where the device performance is determined mainly by the number of molecules in the storage media and not by their position. To exploit the nature of the core-shell POM clusters, we show, at both the molecular and device level, that embedding [(Se(iv)O3)2](4-) as an oxidizable dopant in the cluster core allows the oxidation of the molecule to a [Se(v)2O6](2-) moiety containing a {Se(v)-Se(v)} bond (where curly brackets indicate a moiety, not a molecule) and reveals a new 5+ oxidation state for selenium. This new oxidation state can be observed at the device level, resulting in a new type of memory, which we call 'write-once-erase'. Taken together, these results show that POMs have the potential to be used as a realistic nanoscale flash memory. Also, the configuration of the doped POM core may lead to new types of electrical behaviour. This work suggests a route to the practical integration of configurable molecules in MOS technologies as the lithographic scales approach the molecular limit.
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Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis.
Org. Lett.
PUBLISHED: 06-05-2014
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An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed.
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Effect of Tiotropium on Heart Rate Variability in Stable Chronic Obstructive Pulmonary Disease Patients.
J Aerosol Med Pulm Drug Deliv
PUBLISHED: 05-21-2014
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Abstract Background: The chronic use of the long-acting anticholinergic agent, tiotropium, in chronic obstructive pulmonary disease (COPD) has been linked in some reports to an increase in adverse cardiovascular effects. Decreased heart rate variability (HRV) is a condition seen in COPD patients that has also been linked to poor cardiovascular outcome. We aimed in this study to investigate changes in HRV caused by tiotropium administration to COPD patients in order to determine whether changes occurred that might contribute to an increase in adverse cardiovascular events. Methods: Seventy patients with moderate-to-severe stable COPD were treated with once-daily dosing of tiotropium (two puffs of Spiriva Respimat, 2.5??g solution) for 3 months. HRV, pulmonary function, and quality of life were measured before and after 1 and 3 months of therapy. Results: Pulmonary function and quality of life improved significantly, after both 1 and 3 months of therapy. No significant change in HRV parameters occurred, except for a significant decrease in the high-frequency and increase in the low-frequency component of HRV at the 1-month assessment. Conclusion: Changes in HRV caused by tiotropium use are not sufficient to explain a possible increase in adverse cardiovascular events.
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Addressing the unmet need for visualizing conditional random fields in biological data.
BMC Bioinformatics
PUBLISHED: 04-24-2014
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The biological world is replete with phenomena that appear to be ideally modeled and analyzed by one archetypal statistical framework - the Graphical Probabilistic Model (GPM). The structure of GPMs is a uniquely good match for biological problems that range from aligning sequences to modeling the genome-to-phenome relationship. The fundamental questions that GPMs address involve making decisions based on a complex web of interacting factors. Unfortunately, while GPMs ideally fit many questions in biology, they are not an easy solution to apply. Building a GPM is not a simple task for an end user. Moreover, applying GPMs is also impeded by the insidious fact that the "complex web of interacting factors" inherent to a problem might be easy to define and also intractable to compute upon.
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Exploring the symmetry, structure, and self-assembly mechanism of a gigantic seven-fold symmetric {Pd??} wheel.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 04-23-2014
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The symmetry, structure and formation mechanism of the structurally self-complementary {Pd84} = [Pd84O42(PO4)42(CH3CO2)28](70-) wheel is explored. Not only does the symmetry give rise to a non-closest packed structure, the mechanism of the wheel formation is proposed to depend on the delicate balance between reaction conditions. We achieve the resolution of gigantic polyoxopalladate species through electrophoresis and size-exclusion chromatography, the latter has been used in conjunction with electrospray mass spectrometry to probe the formation of the ring, which was found to proceed by the stepwise aggregation of {Pd6}(-) = [Pd6O4(CH3CO2)2(PO4)3Na(6-n)H(n)](-) building blocks. Furthermore, the higher-order assembly of these clusters into hollow blackberry structures of around 50?nm has been observed using dynamic and static light scattering.
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Guibitang, a traditional herbal medicine, induces apoptotic death in A431 cells by regulating the activities of mitogen-activated protein kinases.
BMC Complement Altern Med
PUBLISHED: 04-22-2014
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Guibi-tang (GBT), a traditional herbal formula, mainly has been shown to possess immune regulation, antioxidant and protective effect of the gastric mucosa. Constituent herbs of GBT are frequently used to treat various diseases; however, their pharmacological effects, especially on cancer cells, differ from those of GBT. Furthermore, the molecular mechanisms behind effects of GBT remain unclear. In the present study, we explored the mechanism of chemopreventive/chemotherapeutic efficacy of GBT against human squamous cell carcinoma without cytotoxicity in normal cells and proved the efficacy of GBT through performing in vivo xenograft assay.
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Step-by-step covalent modification of Cr-templated Anderson-type polyoxometalates.
Dalton Trans
PUBLISHED: 04-04-2014
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A series of tripodal alcohols substituted Anderson-type polyoxometalates (POMs) including mono-substituted (compounds and ), asymmetrical bi-substituted (compound ), and symmetrical bi-substituted ones (compounds and ) have been synthesized under hydrothermal conditions using a pre-designed step-by-step strategy, and compounds , and have been fully characterized by single-crystal X-ray diffraction, ESI-MS, and elemental analysis.
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Deafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-31-2014
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Connexin 26 (Cx26, GJB2) mutations are the major cause of hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. Mouse models show that Cx26 deficiency can cause congenital deafness with cochlear developmental disorders, hair cell degeneration, and the reduction of endocochlear potential (EP) and active cochlear amplification. However, the underlying deafness mechanism still remains undetermined. Our previous studies revealed that hair cell degeneration is not a primary cause of hearing loss. In this study we investigated the role of EP reduction in Cx26 deficiency-induced deafness. We found that the EP reduction is not associated with congenital deafness in Cx26 knockout (KO) mice. The threshold of auditory brainstem response (ABR) in Cx26 KO mice was even greater than 110 dB SPL, demonstrating complete hearing loss. However, the EP in Cx26 KO mice varied and not completely abolished. In some cases, the EP could still remain at higher levels (>70 mV). We further found that the deafness in Cx26 KO mice is associated with cochlear developmental disorders. Deletion of Cx26 in the cochlea before postnatal day 5 (P5) could cause congenital deafness. The cochlea had developmental disorders and the cochlear tunnel was not open. However, no congenital deafness was found when Cx26 was deleted after P5. The cochlea also displayed normal development and the cochlear tunnel was open normally. These data suggest that congenital deafness induced by Cx26 deficiency is not determined by EP reduction and may result from cochlear developmental disorders.
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Effect of serum interleukin 21 on the development of coronary artery disease.
APMIS
PUBLISHED: 03-28-2014
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There has been more and more evidence to confirm the essential role of inflammatory processes in the development of coronary artery disease (CAD). Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the effect of peripheral IL-21 on the pathogenesis and progression of CAD. Serum level of IL-21 in 92 CAD patients and 73 controls was measured by the enzyme-linked immunosorbent assay. Data showed that IL-21 expression was significantly increased in CAD than in controls (p < 0.001). Interestingly, when comparing IL-21 level with different genders, male subjects revealed higher IL-21 than female subjects (p = 0.024). Also, we observed that patients with hypertension had upregulated level of serum IL-21 (p = 0.002). Moreover, serum level of IL-21 was positively correlated with total cholesterol level (p = 0.015) or low-density lipoprotein cholesterol (p = 0.0009) of CAD cases. In addition, we analyzed IL-21 level with the severity of CAD, and identified that cases with 3-vessel affected had significantly elevated level of IL-21 than those with 1-vessel or 2-vessel affected. These data suggested that serum level of IL-21 may be closely associated with the development and progression of CAD.
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Breast cancer awareness among women in Eastern China: a cross-sectional study.
BMC Public Health
PUBLISHED: 03-26-2014
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High breast cancer mortality has been attributed to lack of public awareness, which leads to late diagnoses. As little is known about the level of knowledge and awareness of breast cancer in China, this study was designed to explore it among women in Eastern China.
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Silencing the expression of Cbl-b enhances the immune activation of T lymphocytes against RM-1 prostate cancer cells in vitro.
J Chin Med Assoc
PUBLISHED: 03-18-2014
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The ubiquitin ligase Cbl-b potently modulates T lymphocyte immune responses and is critical in modulating tumor-induced immunosuppression. The influence of Cbl-b in modulating T lymphocyte activity against prostate cancer remains ill defined. We have determined the effects of silencing Cbl-b expression in T lymphocytes and their subsequent cytotoxic activity against prostate cancer cells.
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Effectiveness of a national transitional care program in reducing acute care use.
J Am Geriatr Soc
PUBLISHED: 03-17-2014
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This study evaluated the effectiveness of a national transitional care program for elderly adults with complex care needs and limited social support. The Aged Care Transition (ACTION) Program was designed to improve coordination and continuity of care and reduce rehospitalizations and visits to emergency departments (EDs). Dedicated care coordinators provided coaching to help individuals and families understand the individuals' conditions, effectively articulate their preferences, and enable self-management and care planning. Participants were individuals aged 65 and older hospitalized and enrolled from five public general hospitals in Singapore between February 2009 and July 2010 (N = 4,132). The coordinators worked with participants during hospitalization and followed up with telephone calls and home visits for 1 to 2 months after discharge and coordinated placements with appropriate community service providers. Unplanned rehospitalization and ED visit (up to 6 months after discharge) rates were compared with those of a comparator group of individuals who did not receive care coordination using propensity score-based weighting. Participant and caregiver surveys on quality of life and self-rated health were also administered. Recipients of the ACTION program had fewer unplanned rehospitalizations and ED visits after discharge. Propensity score-adjusted odds ratios of participants versus control for number of unplanned rehospitalization and ED visits were 0.5 (95% confidence interval (CI) = 0.5-0.6) and 0.81 (95% CI = 0.72-0.90) 30 days after discharge and 0.6 (95% CI = 0.6-0.7) and 0.90 (95% CI = 0.82-0.99) 180 days after discharge. Quality of life and self-rated health were better 4 to 6 weeks after discharge than 1 week after discharge. These findings confirm the effectiveness of the ACTION program in improving the transition of vulnerable older adults from hospital to community. Such transitional care should be considered as an integral part of care integration.
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Bioinformatics analysis of alternative polyadenylation in green alga Chlamydomonas reinhardtii using transcriptome sequences from three different sequencing platforms.
G3 (Bethesda)
PUBLISHED: 03-15-2014
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Messenger RNA 3'-end formation is an essential posttranscriptional processing step for most eukaryotic genes. Different from plants and animals where AAUAAA and its variants routinely are found as the main poly(A) signal, Chlamydomonas reinhardtii uses UGUAA as the major poly(A) signal. The advance of sequencing technology provides an enormous amount of sequencing data for us to explore the variations of poly(A) signals, alternative polyadenylation (APA), and its relationship with splicing in this algal species. Through genome-wide analysis of poly(A) sites in C. reinhardtii, we identified a large number of poly(A) sites: 21,041 from Sanger expressed sequence tags, 88,184 from 454, and 195,266 from Illumina sequence reads. In comparison with previous collections, more new poly(A) sites are found in coding sequences and intron and intergenic regions by deep-sequencing. Interestingly, G-rich signals are particularly abundant in intron and intergenic regions. The prevalence of different poly(A) signals between coding sequences and a 3'-untranslated region implies potentially different polyadenylation mechanisms. Our data suggest that the APA occurs in about 68% of C. reinhardtii genes. Using Gene Ontolgy analysis, we found most of the APA genes are involved in RNA regulation and metabolic process, protein synthesis, hydrolase, and ligase activities. Moreover, intronic poly(A) sites are more abundant in constitutively spliced introns than retained introns, suggesting an interplay between polyadenylation and splicing. Our results support that APA, as in higher eukaryotes, may play significant roles in increasing transcriptome diversity and gene expression regulation in this algal species. Our datasets also provide useful information for accurate annotation of transcript ends in C. reinhardtii.
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Polyoxometalate clusters integrated into peptide chains and as inorganic amino acids: solution- and solid-phase approaches.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-12-2014
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General synthetic methods for the grafting of peptide chains onto polyoxometalate clusters by the use of general activated precursors have been developed. Using a solution-phase approach, pre-synthesized peptides can be grafted to a metal oxide cluster to produce hybrids of unprecedented scale (up to 30 residues). An adapted solid-phase method allows the incorporation of these clusters, which may be regarded as novel hybrid unnatural amino acids, during the peptide synthesis itself. These methods may open the way for the automated synthesis of peptides and perhaps even proteins that contain "inorganic" amino acids.
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Time-resolved assembly of cluster-in-cluster {Ag??}-in-{W??} polyoxometalates under supramolecular control.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-02-2014
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We report the time-resolved supramolecular assembly of a series of nanoscale polyoxometalate clusters (from the same one-pot reaction) of the form: [H(10+m)Ag18Cl(Te3W38O134)2]n, where n=1 and m=0 for compound 1 (after 4?days), n=2 and m=3 for compound 2 (after 10?days), and n=? and m=5 for compound 3 (after 14?days). The reaction is based upon the self-organization of two {Te3W38} units around a single chloride template and the formation of a {Ag12} cluster, giving a {Ag12}-in-{W76} cluster-in-cluster in compound 1, which further aggregates to cluster compounds 2 and 3 by supramolecular Ag-POM interactions. The proposed mechanism for the formation of the clusters has been studied by ESI-MS. Further, control experiments demonstrate the crucial role that TeO3(2-), Cl(-), and Ag(+) play in the self-assembly of compounds 1-3.
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Assembly and core transformation properties of two tetrahedral clusters: [Fe(III)13P8W60O227(OH)15(H2O)2]30- and [Fe(III)13P8W60O224(OH)12(PO4)4]33-.
Dalton Trans
PUBLISHED: 02-12-2014
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Two nanosized 2.6 nm Fe(III) substituted polyoxotungstates [Fe(III)13P8W60O227(OH)15(H2O)2](30-) (1) and [Fe(III)13P8W60O224(OH)12(PO4)4](33-) (2) are presented herein. Both clusters are synthesized from the reactions of trilacunary polyoxotungstate precursor [?-P2W15O56](12-) and FeCl3 under strict pH control at atmospheric pressure. The compounds are fully characterised in the solid state (FTIR and single-crystal XRD, elemental and thermogravimetric analyses), solution (cyclic voltammetry and UV-Vis spectroscopy) and in the gas phase (ESI-MS). An {Fe(III)13} core is present in both clusters which can be described as Archimedean solids (truncated tetrahedron, 1; elongated cuboctahedron, 2). 1 shows iron delivery properties coupled to a K(+)-triggered transformation of the {Fe13} core to a {K?Fe12} core in solution. Cyclic voltammetry shows the presence of independent W- and Fe-centred redox processes that support the stability of the clusters in solution. ESI-MS analyses confirm further the stability of 1 and 2 in the gas phase.
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SIRT1 activation by a c-MYC oncogenic network promotes the maintenance and drug resistance of human FLT3-ITD acute Myeloid Leukemia stem cells.
Cell Stem Cell
PUBLISHED: 02-04-2014
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The FLT3-ITD mutation is frequently observed in acute myeloid leukemia (AML) and is associated with poor prognosis. In such patients, FLT3 tyrosine kinase inhibitors (TKIs) are only partially effective and do not eliminate the leukemia stem cells (LSCs) that are assumed to be the source of treatment failure. Here, we show that the NAD-dependent SIRT1 deacetylase is selectively overexpressed in primary human FLT3-ITD AML LSCs. This SIRT1 overexpression is related to enhanced expression of the USP22 deubiquitinase induced by c-MYC, leading to reduced SIRT1 ubiquitination and enhanced stability. Inhibition of SIRT1 expression or activity reduced the growth of FLT3-ITD AML LSCs and significantly enhanced TKI-mediated killing of the cells. Therefore, these results identify a c-MYC-related network that enhances SIRT1 protein expression in human FLT3-ITD AML LSCs and contributes to their maintenance. Inhibition of this oncogenic network could be an attractive approach for targeting FLT3-ITD AML LSCs to improve treatment outcomes.
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Effect of supersaturation on hillock of directional Growth of KDP crystals.
Sci Rep
PUBLISHED: 01-20-2014
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KDP single crystals were grown in aqueous solution by using "point seeds" with a defined crystallographic direction of 59° to the Z axis. When hillock slopes on the (100) face of KDP crystals were measured within the supersaturation (?) range of 0 < ? ? 0.06, the slope of hillocks with hollow cores depended nonlinearly on supersaturation. Below ? = 0.02, the hillock slope depended on supersaturation, but when ? was ? 0.02, the hillock slope increased more gradually and was less dependent on supersaturation. Hollow funnel-shaped growth dislocation on the (100) face of KDP crystals was observed at ? = 0.04, characterized by large holes with micro-steps and step bunching inside, the formation of which were analyzed. The result verified that the reversed growth appears to occur within hollow channels found on growth hillocks.
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Towards imaging electron density inside metal-organic framework structures.
Chem. Commun. (Camb.)
PUBLISHED: 01-17-2014
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Herein, we present electron density maps of three MOFs with different guests or post-synthetic modifications produced using single crystal X-ray data from laboratory diffractometers. Analysis of the electron density maps reveals possible differences inside the pores indicating that this approach may be used to explore frameworks using inexpensively gained X-ray data.
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Association of miR-146a gene polymorphism with risk of nasopharyngeal carcinoma in the central-southern Chinese population.
J. Hum. Genet.
PUBLISHED: 01-16-2014
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This case-control study focused on estimating the association between miR-146a polymorphism and risk of nasopharyngeal carcinoma (NPC) in central-south China. In total, 160 patients with NPC and 200 healthy controls in central-south China were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay. Chi-square test was used to assess the different distribution of miR-146a polymorphism between NPC patients and controls; and logistic regression analysis was applied to analyze the associations between miR-146a polymorphism with cancer risk in different contrast models. Significant differences between NPC patients and controls were found in genotype (P=0.033 for GG versus CG versus CC; and odds ratio (OR)=0.568, 95% confidence interval (CI)=0.354-0.912, P=0.019 for CG versus CC; and OR=0.503, 95% CI=0.261-0.971, P=0.041 for CG versus CC; and OR=0.564, 95% CI=0.360-0.884, P=0.012 for GG+CG versus CC, respectively) and allelic analysis (P=0.025 for G versus C). Our findings suggested that polymorphism of mir-146a was associated with NPC in the central-southern Chinese population.
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Checkpoint kinase 1 is negatively regulated by miR-497 in hepatocellular carcinoma.
Med. Oncol.
PUBLISHED: 01-15-2014
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Checkpoint kinase 1 (CHEK1) is an evolutionarily conserved Ser/Thr kinase, which mediates cell-cycle arrest after DNA damage, and we previously reported that CHEK1 was overexpressed and associated with poor prognosis in hepatocellular carcinoma (HCC), indicating it was oncogenic gene. In this study, we aimed to elucidate the mechanism of CHEK1 overexpression in HCC. We first verified the upregulated CHEK1 by qRT-PCR and western blot in 30 HCC samples compared with corresponding non-tumor liver tissues. In silico analysis showed that CHEK1 was a candidate target of miR-497, which was previously found to be downregulated in HCC by us. To test whether miR-497 could bind to 3'untranslated region (3'UTR) of CHEK1, luciferase reporter assay was conducted. The result revealed that miR-497 could bind to the 3'untranslated region (3'UTR) of CHEK1 mRNA. Western blot showed that ectopic expression of miR-497 suppressed the CHEK1 expression and inhibition of miR-497 led to significant upregulation of CHEK1. Finally, miR-497 expression was measured in the same 30 HCC samples, and the correlation between miR-497 and CHEK1 was analyzed. The results indicated that miR-497 was downregulated in HCC and had a significant negative correlation with CHEK1. Taken together, these results demonstrated that CHEK1 was negatively regulated by miR-497, and the overexpressed CHEK1 was resulted from the downregulated miR-497 in HCC, which provided a potential molecular target for HCC therapy.
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Formation, self-assembly and transformation of a transient selenotungstate building block into clusters, chains and macrocycles.
Chem. Commun. (Camb.)
PUBLISHED: 01-15-2014
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The one-pot syntheses of a series of dimeric and trimeric selenotungstates based on the [Se2W12O46](12-) unit are presented alongside the structure of the tetrameric [Se8W48O176](32-) wheel. Mass spectrometry has probed the stability of these clusters whilst their electronic structure has been contrasted to their known phosphotungstate analogues.
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SCOPE++: sequence classification of homoPolymer emissions.
Genomics
PUBLISHED: 01-09-2014
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mRNA polyadenylation, the addition of a poly(A) tail to the 3'-end of pre-mRNA, is a process critical to gene expression and regulation in eukaryotes. To understand the molecular mechanisms governing polyadenylation and other relevant biological processes, it is important to identify these poly(A) tails accurately in transcriptome sequencing data and differentiate them from artificial adapter sequences added in the sequencing process. But the annotation of these tails is complicated by the presence of sequencing errors and post-transcriptional modifications. While determining that a tail is present in a given transcript fragment is straight-forward, these obfuscations make the problem of boundary identification a challenge; conventional seed-and-extend algorithms struggle to accurately identify these poly(A) tail end-points. Further, all existing tools that we are aware of focus exclusively on the trimming of poly(A) tails, failing to provide the detailed information needed for studying the polyadenylation process.
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detectIR: A Novel Program for Detecting Perfect and Imperfect Inverted Repeats Using Complex Numbers and Vector Calculation.
PLoS ONE
PUBLISHED: 01-01-2014
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Inverted repeats are present in abundance in both prokaryotic and eukaryotic genomes and can form DNA secondary structures - hairpins and cruciforms that are involved in many important biological processes. Bioinformatics tools for efficient and accurate detection of inverted repeats are desirable, because existing tools are often less accurate and time consuming, sometimes incapable of dealing with genome-scale input data. Here, we present a MATLAB-based program called detectIR for the perfect and imperfect inverted repeat detection that utilizes complex numbers and vector calculation and allows genome-scale data inputs. A novel algorithm is adopted in detectIR to convert the conventional sequence string comparison in inverted repeat detection into vector calculation of complex numbers, allowing non-complementary pairs (mismatches) in the pairing stem and a non-palindromic spacer (loop or gaps) in the middle of inverted repeats. Compared with existing popular tools, our program performs with significantly higher accuracy and efficiency. Using genome sequence data from HIV-1, Arabidopsis thaliana, Homo sapiens and Zea mays for comparison, detectIR can find lots of inverted repeats missed by existing tools whose outputs often contain many invalid cases. detectIR is open source and its source code is freely available at: https://sourceforge.net/projects/detectir.
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Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Case-Control Study and Meta-Analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.
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Development of aminoglycoside and ?-lactamase resistance among intestinal microbiota of swine treated with lincomycin, chlortetracycline, and amoxicillin.
Front Microbiol
PUBLISHED: 01-01-2014
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Lincomycin, chlortetracycline, and amoxicillin are commonly used antimicrobials for growth promotion and infectious disease prophylaxis in swine production. In this study, we investigated the shifts and resistance development among intestinal microbiota in pregnant sows before and after lincomycin, chlortetracycline, and amoxicillin treatment by using phylogenetic analysis, bacterial enumeration, and PCR. After the antimicrobial treatment, shifts in microbial community, an increased proportion of resistant bacteria, and genes related to antimicrobial resistance as compared to the day before antimicrobial administration (day 0) were observed. Importantly, a positive correlation between antimicrobial resistance gene expression in different categories, especially those encoding aminoglycoside and ?-lactamase and antimicrobial resistance, was observed. These findings demonstrate an important role of antimicrobial usage in animals in the development of antimicrobial resistance, and support the notion that prudent use of antimicrobials in swine is needed to reduce the risk of the emergence of multi-drug resistant zoonotic pathogens.
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Aging Increases the Susceptivity of MSCs to Reactive Oxygen Species and Impairs Their Therapeutic Potency for Myocardial Infarction.
PLoS ONE
PUBLISHED: 01-01-2014
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Myocardial infarction (MI) is one of the leading causes of death worldwide and Mesenchymal Stem Cells (MSCs) transplantation has been considered a promising therapy. Recently, it was reported that the therapeutic effectiveness of MSCs is dependent on the age of the donor, yet the underlying mechanism has not been thoroughly investigated. This study was designed to investigate whether this impaired therapeutic potency is caused by an increased susceptivity of MSCs from old donors to reactive oxygen species (ROS). The MSCs were isolated from the subcutaneous inguinal region of young (8-10 weeks) and old (18 months) Sprague-Dawley (SD) rats. By exposing these MSCs to H2O2, we found that the adhesion of MSCs from old donors was damaged more severely. Specifically, decreased expression of integrin and reduced phosphorylation of focal adhesion kinase Src and FAK were observed. Furthemore, H2O2 triggered an increased apoptosis of MSCs from old donors. To study the viability and therapeutic potency of MSCs from young and old donors in vivo, these MSCs were transplanted into acute MI model rats. We observed a more rapidly decreased survival rate of the old MSCs in the infarct region, which may be caused by their increased susceptivity to the micro-environmental ROS, as transplantation of the old MSCs with N-acetyl-L-cysteine (NAC), a ROS scavenger, protected them. The low viability of engrafted old MSCs consequently impaired their therapeutic effectiveness, judging by the histology and function of heart. Our study may help to understand the mechanism of MSCs-host interaction during MI, as well as shed light on the design of therapeutic strategy in clinic.
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Survey of tuberculosis hospitals in china: current status and challenges.
PLoS ONE
PUBLISHED: 01-01-2014
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Hospitals will play an increasingly important role in delivering TB services in China, however little is known in terms of the current landscape of the hospital system that delivers TB care.
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Visualization-aided classification ensembles discriminate lung adenocarcinoma and squamous cell carcinoma samples using their gene expression profiles.
PLoS ONE
PUBLISHED: 01-01-2014
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The widespread application of microarray experiments to cancer research is astounding including lung cancer, one of the most common fatal human tumors. Among non-small cell lung carcinoma (NSCLC), there are two major histological types of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC).
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Absence of Gamma-Interferon-Inducible Lysosomal Thiol Reductase (GILT) Is Associated with Poor Disease-Free Survival in Breast Cancer Patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Tumor immunosurveillance is known to be of critical importance in controlling tumorigenesis and progression in various cancers. The role of gamma-interferon-inducible lysosomal thiol reductase (GILT) in tumor immunosurveillance has recently been studied in several malignant diseases, but its role in breast cancer remains to be elucidated. In the present study, we found GILT as a significant different expressed gene by cDNA microarray analysis. To further determine the role of GILT in breast cancer, we examined GILT expression in breast cancers as well as noncancerous breast tissues by immunohistochemistry and real-time PCR, and assessed its association with clinicopathologic characteristics and patient outcome. The absence of GILT expression increased significantly from 2.02% (2/99) in noncancerous breast tissues to 15.6% (34/218) in breast cancer tissues (P<0.001). In accordance with its proliferation inhibiting function, GILT expression was inversely correlated with Ki67 index (P<0.05). In addition, absence of GILT was positively correlated with adverse characteristics of breast cancers, such as histological type, tumor size, lymph nodes status, and pTNM stage (P<0.05). Consistently, breast cancers with reduced GILT expression had poorer disease-free survival (P<0.005). Moreover, significantly decreased expression of GILT was found in both primary and metastatic breast cancer cells, in contrast to normal epithelial cells. These findings indicate that GILT may act as a tumor suppressor in breast cancer, in line with its previously suggested role in anti-tumor immunity. Thus, GILT has the potential to be a novel independent prognostic factor in breast cancer and further studies are needed to illustrate the underlying mechanism of this relationship.
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Diagnostic delay of pulmonary nontuberculous mycobacterial infection in China.
Multidiscip Respir Med
PUBLISHED: 01-01-2014
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Nontuberculous mycobacteria (NTM) infection is an emerging, but neglected public health concern in China.
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The meganuclease I-SceI containing nuclear localization signal (NLS-I-SceI) efficiently mediated mammalian germline transgenesis via embryo cytoplasmic microinjection.
PLoS ONE
PUBLISHED: 01-01-2014
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The meganuclease I-SceI has been effectively used to facilitate transgenesis in fish eggs for nearly a decade. I-SceI-mediated transgenesis is simply via embryo cytoplasmic microinjection and only involves plasmid vectors containing I-SceI recognition sequences, therefore regarding the transgenesis process and application of resulted transgenic organisms, I-SceI-mediated transgenesis is of minimal bio-safety concerns. However, currently no transgenic mammals derived from I-SceI-mediated transgenesis have been reported. In this work, we found that the native I-SceI molecule was not capable of facilitating transgenesis in mammalian embryos via cytoplasmic microinjection as it did in fish eggs. In contrast, the I-SceI molecule containing mammalian nuclear localization signal (NLS-I-SceI) was shown to be capable of transferring DNA fragments from cytoplasm into nuclear in porcine embryos, and cytoplasmic microinjection with NLS-I-SceI mRNA and circular I-SceI recognition sequence-containing transgene plasmids resulted in transgene expression in both mouse and porcine embryos. Besides, transfer of the cytoplasmically microinjected mouse and porcine embryos into synchronized recipient females both efficiently resulted in transgenic founders with germline transmission competence. These results provided a novel method to facilitate mammalian transgenesis using I-SceI, and using the NLS-I-SceI molecule, a simple, efficient and species-neutral transgenesis technology based on embryo cytoplasmic microinjection with minimal bio-safety concerns can be established for mammalian species. As far as we know, this is the first report for transgenic mammals derived from I-SceI-mediated transgenesis via embryo cytoplasmic microinjection.
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YouGenMap: a web platform for dynamic multi-comparative mapping and visualization of genetic maps.
Front Genet
PUBLISHED: 01-01-2014
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Comparative genetic maps are used in examination of genome organization, detection of conserved gene order, and exploration of marker order variations. YouGenMap is an open-source web tool that offers dynamic comparative mapping capability of users' own genetic mapping between 2 or more map sets. Users' genetic map data and optional gene annotations are uploaded, either publically or privately, as long as they follow our template which is available in several standard file formats. Data is parsed and loaded into MySQL relational database to be displayed and compared against users' genetic maps or other public data available on YouGenMap. With the highly interactive GUIs, all public data on YouGenMap are maps available for visualization, comparison, search, filtration and download. YouGenMap web tool is available on the website (http://conifergdb.miamioh.edu/yougenmap) with the source-code repository at (http://sourceforge.net/projects/yougenmap/?source=directory).
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Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine.
Nat Commun
PUBLISHED: 01-01-2014
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The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical 'real-space' search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo(2)O(2)S(2)](2+)-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo(10)(C5)}; 2, {Mo(14)(C4)4(C5)2}; 3, {Mo(60)(C4)10}; 4, {Mo(48)(C4)6}; 5, {Mo(34)(C4)4}; 6, {Mo(18)(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations.
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A MATLAB-based tool for accurate detection of perfect overlapping and nested inverted repeats in DNA sequences.
Bioinformatics
PUBLISHED: 11-08-2013
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Palindromic sequences, or inverted repeats (IRs), in DNA sequences involve important biological processes such as DNA-protein binding, DNA replication and DNA transposition. Development of bioinformatics tools that are capable of accurately detecting perfect IRs can enable genome-wide studies of IR patterns in both prokaryotes and eukaryotes. Different from conventional string-comparison approaches, we propose a novel algorithm that uses a cumulative score system based on a prime number representation of nucleotide bases. We then implemented this algorithm as a MATLAB-based program for perfect IR detection. In comparison with other existing tools, our program demonstrates a high accuracy in detecting nested and overlapping IRs.Availability and implementation: The source code is freely available on (http://bioinfolab.miamioh.edu/bioinfolab/palindrome.php) CONTACT: liangc@miamioh.edu or karroje@miamioh.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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A redox-triggered structural rearrangement in an iodate-templated polyoxotungstate cluster cage.
Chem. Commun. (Camb.)
PUBLISHED: 09-12-2013
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The new tungstatoiodate, ?-[H5W18O59(IO3)](6-), containing I(V)O3(-) within a {W18O54} metal oxide framework has been prepared and shown by X-ray crystallography and mass spectrometry to be derived from the fully oxidised [H3W18O56(IO6)](6-) by two-electron reduction accompanied by a redox-triggered structural rearrangement where three I-O covalent bonds are broken.
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Exploring the assembly of supramolecular polyoxometalate triangular morphologies with Johnson solid cores: [(Mn(II)(H2O)3)2(K?{?-GeW10Mn(II)2O38}3)]19-.
Inorg Chem
PUBLISHED: 07-26-2013
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A new polyoxometalate (POM) cluster compound is presented which incorporates a trimeric assembly of Keggin-type germanotungstate fragments trapping a Johnson-type solid {Mn8} core. The mixed K-Li salt of the polyanion [(Mn(II)(H2O)3)2(K?{?-GeW10Mn(II)2O38}3)](19-) was characterized in the solid state and solution. The correlation of the assembly processes and the observed architecture of the "trinity" family of POMs is discussed.
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Quick and selective synthesis of Li6[?-P2W18O62]·28H2O soluble in various organic solvents.
Dalton Trans
PUBLISHED: 07-08-2013
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Herein we report the synthesis of ?-Dawson type POM, Li6[?-P2W18O62]·28H2O, directly from the use of Li2WO4 as the tungstate source. The salt obtained was soluble not only in water but also in a range of polar and non-polar organic solvents, such as benzene.
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Comparative analysis of error-prone replication mononucleotide repeats across baculovirus genomes.
Virus Res.
PUBLISHED: 07-06-2013
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Genome replication by the baculovirus DNA polymerase often generates errors in mononucleotide repeat (MNR) sequences due to replication slippage. This results in the inactivation of genes that affects different stages of the cell infection cycle. Here we mapped these MNRs in the 59 baculovirus genomes. We found that the MNR frequencies of baculovirus genomes are different and not correlated with the genome sizes. Although the average A/T content of baculoviruses is 58.67%, the A/T MNR frequency is significantly higher than that of the G/C MNRs. Furthermore, the A7/T7 MNRs are the most frequent of those we studied. Finally, MNR frequencies in different classes of baculovirus genes, such as immediate early genes, show differences between baculovirus genomes, suggesting that the distribution and frequency of different MNRs are unique to each baculovirus species or strain. Therefore, the results of this study can help select appropriate baculoviruses for the development of biological insecticides.
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Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma.
Clin. Cancer Res.
PUBLISHED: 06-28-2013
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MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma and delineate their clinical significance for hepatocellular carcinoma.
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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.

Video X seems to be unrelated to Abstract Y...

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.