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Find video protocols related to scientific articles indexed in Pubmed.
Three-dimensionalization of ultrathin nanosheets in a two-dimensional nano-reactor: macroporous CuO microstructures with enhanced cycling performance.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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Three-dimensional (3D) macroporous CuO structures composed of ultrathin nanosheets were successfully synthesized by employing a liquid-liquid interface as a two-dimensional (2D) nano-reactor. The macroporous structure helped CuO to retain the exposed surface during reactions, thus significantly enhancing the long term cycling performance both in photocatalysis and lithium ion batteries.
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Modeling Linear and Cyclic PKS Intermediates through Atom Replacement.
J. Am. Chem. Soc.
PUBLISHED: 11-20-2014
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The mechanistic details of many polyketide synthases (PKSs) remain elusive due to the instability of transient intermediates that are not accessible via conventional methods. Here we report an atom replacement strategy that enables the rapid preparation of polyketone surrogates by selective atom replacement, thereby providing key substrate mimetics for detailed mechanistic evaluations. Polyketone mimetics are positioned on the actinorhodin acyl carrier protein (actACP) to probe the underpinnings of substrate association upon nascent chain elongation and processivity. Protein NMR is used to visualize substrate interaction with the actACP, where a tetraketide substrate is shown not to bind within the protein, while heptaketide and octaketide substrates show strong association between helix II and IV. To examine the later cyclization stages, we extended this strategy to prepare stabilized cyclic intermediates and evaluate their binding by the actACP. Elongated monocyclic mimics show much longer residence time within actACP than shortened analogs. Taken together, these observations suggest ACP-substrate association occurs both before and after ketoreductase action upon the fully elongated polyketone, indicating a key role played by the ACP within PKS timing and processivity. These atom replacement mimetics offer new tools to study protein and substrate interactions and are applicable to a wide variety of PKSs.
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Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.
Gut
PUBLISHED: 11-20-2014
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Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population.
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Investigation of anti-oxidative stress in vitro and water apparent diffusion coefficient in MRI on rat after spinal cord injury in vivo with Tithonia diversifolia ethanolic extracts treatment.
BMC Complement Altern Med
PUBLISHED: 11-18-2014
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Spinal cord injury (SCI)-induced secondary oxidative stress associates with a clinical complication and high mortality. Treatments to improve the neurological outcome of secondary injury are considered as important issues. The objective of the current study is to evaluate the anti-oxidative effect of Tithonia diversifolia ethanolic extracts (TDE) on cells and apply the pharmacological effect to SCI model using a MRI imaging algorism.
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SFTS virus infection in non-human primates.
J. Infect. Dis.
PUBLISHED: 10-19-2014
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SFTS virus (SFTSV) is a highly pathogenic bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease in China. Laboratory mice have been reported to be susceptible to SFTSV infection, but the infection of SFTSV in non-human primates (NHPs) has not been investigated. This study is the first to report that SFTSV does not cause severe symptoms or death in rhesus macaques, but causes fever, thrombocytopenia, leukocytopenia, as well as raised levels of transaminases and myocardial enzymes in blood. Viremia, virus specific IgM and IgG antibodies, and neutralizing antibodies were identified in all infected macaques. The cytokines interferon-?, eotaxin, TNF-?, and MIP-1? were significantly elevated in the blood. Minor pathological lesions were observed in the liver and kidney in late stages of infection. Overall, SFTSV infection in rhesus macaques resembled a mild SFTS disease in humans.
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Assessment of the internal genes of influenza A (H7N9) virus contributing to the high pathogenicity in mice.
J. Virol.
PUBLISHED: 10-17-2014
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The recently identified H7N9 influenza A virus has caused severe economic losses and worldwide public concern. Genetic analysis indicates that its six internal genes all originated from H9N2 viruses. However, the H7N9 virus is more highly pathogenic in humans than H9N2, which suggests that the internal genes of H7N9 have mutated. To analyze which H7N9 virus internal genes contribute to its high pathogenicity, a series of reassortants were generated by reverse genetics, each containing a single internal gene of the typical A/Anhui/1/2013(H7N9) virus in the genetic background of the A/chicken/Shandong/lx1023/2007(H9N2) virus. Their replication ability, polymerase activity, and pathogenicity were then evaluated in vitro and in vivo. These recombinants displayed high genetic compatibility, and the H7N9-derived PB2, M, and NP genes were identified as the virulence genes for the reassortants in mice. Further investigation confirmed PB2-K627 is critical for the high pathogenicity of the H7N9 virus and the reassortant containing the H7N9-derived PB2 segment (H9N2-AH/PB2). Notably, the H7N9-derived PB2 gene displayed a greater compatibility with the H9N2 genome than that of H7N9, endowing the H9N2-AH/PB2 reassortant with greater viability and virulence than the parental H7N9 virus. In addition, the H7N9 virus, with the exception of the H9N2 reassortants, could effectively replicate in human A549 cells. Our results indicate that PB2, M, and NP are the key virulence genes, together with the surface HA and NA proteins, contributing to the high infectivity of the H7N9 virus in humans.
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Transmission of H7N9 influenza virus in mice by different infective routes.
Virol. J.
PUBLISHED: 10-03-2014
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On 19 February 2013, the first patient infected with a novel influenza A H7N9 virus from an avian source showed symptoms of sickness. More than 349 laboratory-confirmed cases and 109 deaths have been reported in mainland China since then. Laboratory-confirmed, human-to-human H7N9 virus transmission has not been documented between individuals having close contact; however, this transmission route could not be excluded for three families. To control the spread of the avian influenza H7N9 virus, we must better understand its pathogenesis, transmissibility, and transmission routes in mammals. Studies have shown that this particular virus is transmitted by aerosols among ferrets.
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Combinations of Oseltamivir and Fibrates Prolong the Mean Survival Time of Mice Infected with the Lethal H7N9 Influenza Virus.
J. Gen. Virol.
PUBLISHED: 10-03-2014
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The outbreak of human infections caused by the novel avian-origin H7N9 influenza viruses in China since March 2013 underscores the urgent need to find an effective treatment strategy against H7N9 infection in humans. In this study, we assessed the effectiveness of combinations of oseltamivir and two immunomodulators, simvastatin and fenofibrate, against H7N9 infection in a mouse model. Mice treated with oseltamivir plus fenofibrate exhibited the longest mean survival time, the largest reduction of viral titer in lung tissue, the highest levels of CD4+ and CD8+ T lymphocytes, and the greatest decrease in pulmonary inflammation. Thus, the combination of oseltamivir plus fenofibrate improved the outcomes of mice infected with H7N9 virus by simultaneously reducing viral replication and normalizing the aberrant immune response. This drug combination should be considered in randomized controlled trials of treatments for H7N9 patients.
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Monocrystalline mesoporous metal oxide with perovskite structure: a facile solid-state transformation of a coordination polymer.
Chem. Commun. (Camb.)
PUBLISHED: 09-27-2014
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Monocrystalline mesoporous BiFeO3 crystals were obtained via a multi-step single-crystal to single-crystal transformation of a coordination polymer, Bi[Fe(CN)6]·4H2O. This unique transformation process significantly decreased the crystallization temperature of perovskite oxide without losing high crystallinity.
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Preclinical safety evaluation of human mesenchymal stem cell transplantation in cerebrum of nonhuman primates.
Int. J. Toxicol.
PUBLISHED: 08-17-2014
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The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 × 10(5) cells/kg), high dose (2.5 × 10(6) cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS were injected into each monkey for 2 times, with an interval of 3 weeks. The injection point was located outside of the right putamen, according to a stereotactic map and preoperative magnetic resonance imaging of the monkeys. Animal health, behavior, biophysical and biochemical parameters, and brain neurological function were routinely monitored over a 6-month period posttransplantation, and the histopathologic examinations were also performed. The results showed that local pathologic damage including local tissue necrosis and inflammation was induced after the injection. The damage of low-dose and high-dose groups was greater than that of the control group, yet over time, the damage could be repaired gradually. No major hMSCs-associated changes were induced from other indicators, and the transplantation of hMSCs in monkeys did not affect total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore conclude that transplantation of hMSCs to the cerebrum represents a safe alternative for clinical application of neurological disorders.
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Clinical applications of the indirect immunofluorescence assay for detection of anti-cell membrane-associated DNA antibodies in Juvenile Systemic Lupus Erythematosus.
Pediatr. Res.
PUBLISHED: 08-15-2014
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BackgroundJuvenile-onset systemic lupus erythematosus (JSLE) has a higher mortality risk compared to adult-onset SLE. We compared the diagnostic value of anti-cmDNA antibodies with that of anti-nucleosome antibodies (AnuA), anti-Sm antibodies and anti-dsDNA antibodies and human B lymphocyte Raji cells with that of human promyelocytic leukemia HL60 cells as substrates in an indirect immunofluorescence assay to detect anti-cmDNA antibodies in JSLE patients.MethodsWe recruited 92 JSLE patients and 71 patients with other rheumatic diseases. Anti-cmDNA antibodies and ANA were detected in patient sera using indirect immunofluorescence assays. Anti-dsDNA antibodies were detected by combining ELISA and indirect immunofluorescence. Anti-Sm antibodies were detected by double immunodiffusion assay and immunoblotting, while anti-nucleosome antibodies (AnuA) were detected by ELISA.ResultsJSLE group had a significantly higher percentage of patients positive for anti-cmDNA compared to patients with other rheumatoid diseases. Using one antibody for diagnosis, anti-cm DNA antibodies has highest accuracy as 84.0%, using 2 antibodies, the combination of anti-cm DNA and anti-dsDNA antibodies has 90.8 % accuracy. Raji cells used as substrate demonstrated a stronger intensity of fluorescent patterns compared to HL60 cells.ConclusionThe high sensitivity, specificity and accuracy of detection of anti-cmDNA antibodies make it a valuable diagnostic tool for JSLE.Pediatric Research (2014); doi:10.1038/pr.2014.182.
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Iridium complexes of new NCP pincer ligands: catalytic alkane dehydrogenation and alkene isomerization.
Chem. Commun. (Camb.)
PUBLISHED: 08-07-2014
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Iridium complexes of novel NCP pincer ligands containing pyridine and phosphinite arms have been synthesized. One Ir complex shows good catalytic activity for alkane dehydrogenation, and all complexes are highly active for olefin isomerization. A combination of the Ir complex and a (PNN)Fe pincer complex catalyzes the formation of linear alkylboronates selectively from internal olefins via sequential olefin isomerization-hydroboration.
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PB2-E627K and PA-T97I substitutions enhance polymerase activity and confer a virulent phenotype to an H6N1 avian influenza virus in mice.
Virology
PUBLISHED: 07-25-2014
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H6N1 avian influenza viruses (AIVs) may pose a potential human risk as suggested by the first documented naturally-acquired human H6N1 virus infection in 2013. Here, we set out to elucidate viral determinants critical to the pathogenesis of this virus using a mouse model. We found that the recombinant H6N1 viruses possessing both the PA-T97I and PB2-E627K substitutions displayed the greatest enhancement of replication in vitro and in vivo. Polymerase complexes possessing either PB2-E627K, PA-T97I, and PB2-E627K/PA-T97I displayed higher virus polymerase activity when compared to the wild-type virus, which may account for the increased replication kinetics and enhanced virulence of variant viruses. Our results demonstrate that PB2-E627K and PA-T97I enhance the ability of H6N1 virus to replicate and cause disease in mammals. Influenza surveillance efforts should include scrutiny of these regions of PB2 and PA because of their impact on the increased virulence of H6N1 AIVs in mice.
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Differential expression and regulation of Ido2 in the mouse uterus during peri-implantation period.
In Vitro Cell. Dev. Biol. Anim.
PUBLISHED: 07-22-2014
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Ido2 is involved in tryptophan catabolism and immunity, but its physiological functions remain poorly understood. This study was undertaken to examine the expression and regulation of Ido2 gene in mouse uterus during the peri-implantation period. The results showed that Ido2 mRNA was highly expressed on day 4 of pregnancy and in the delayed implantation uterus. On days 5-8 of pregnancy, a low level of Ido2 expression was observed in the uteri. Simultaneously, Ido2 mRNA was also lowly expressed in the decidualized uterus. In the uterine stromal cells, 8-Br-cAMP could inhibit the expression of Ido2 mRNA. Moreover, Ido2 mRNA expression was gradually decreased after the stromal cells were treated with estrogen and progesterone and reached a nadir at 96 h. Further study found that overexpression of Ido2 could downregulate the expression of decidualization marker genes PRL, IGFBP1, and Dtprp under in vitro decidualization, while inhibition of Ido2 with devo-1-methyl-tryptophan (D-1-MT) could upregulate the expression of these marker genes. Under in vitro decidualization, overexpression of Ido2 could suppress the proliferation of uterine stromal cells and elevate the expression of Bax and MMP2 genes. On the contrary, Ido2 inhibitor D-1-MT could enhance the proliferation of stromal cells and expression of Bcl2 gene but decline the Bax/Bcl2 ratio. In the uterine stromal cells, estrogen and progesterone could induce the expression of Ido2 mRNA. These data indicate that Ido2 may be important for mouse embryo implantation and decidualization.
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Valproate improves memory deficits in an Alzheimer's disease mouse model: investigation of possible mechanisms of action.
Cell. Mol. Neurobiol.
PUBLISHED: 06-18-2014
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Alzheimer's disease (AD) is a very common progressive neurodegenerative disorder affecting the learning and memory abilities in the brain. Key findings from recent studies of epigenetic mechanisms of memory suggest chromatin remodeling disorders via histone hypoacetylation of the lysine residue contribute to the cognitive impairment in AD. Therefore, the deinhibition of histone acetylation induced by histone deacetylases (HDACs) inhibitors contributes to recovery of learning and memory. We show here that the antiepileptic drug sodium valproate (VPA) potently enhanced long-term recognition memory and spatial learning and memory in AD transgenic mice. Possible mechanisms showed VPA could significantly elevate histone acetylation through HDACs activity inhibition and increase plasticity-associated gene expression within the hippocampi of mice. Our study suggests that VPA, serving as a HDACs inhibitor, can be considered as a potential pharmaceutical agent for the improvement of cognitive function in AD.
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Characterization of antiproliferative activity constituents from Artocarpus heterophyllus.
J. Agric. Food Chem.
PUBLISHED: 06-04-2014
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Artocarpus heterophyllus is an evergreen fruit tree cultivated in many tropical regions. Previous studies have shown that some of its compositions exhibited potential tyrosinase inhibition activities. This study indentified 8 new phenolic compounds, artoheterophyllins E-J (1-6), 4-geranyl-2',3,4',5-tetrahydroxy-cis-stilbene (7), and 5-methoxymorican M (8) and 2 new natural compounds (9 and 10), 2,3-dihydro-5,7-dihydroxy-2-(2-hydroxy-4-methoxyphenyl)-4H-benzopyran-4-one and 6-[(1S,2S)-1,2-dihydroxy-3-methylbutyl]-2-(2,4-dihydroxyphenyl)-5-hydroxy-7-methoxy-3-(3-methyl-2-buten-1-yl)-4H-1-benzopyran-4-one, together with 23 known compounds (11-33), from the ethanol extract of the wood of A. heterophyllus. The structures of the eight new compounds (1-8) and two new natural compounds were established by extensive 1D- and 2D-NMR experiments. The anticancer effects of the isolated compounds were examined in MCF-7, H460, and SMMC-7721 human cancer cell lines by MTT assay. Compounds 5, 11, 12, and 30 significantly reduced the cell viabilities of these cell lines. Especially, compounds 11 and 30 resulted in more potent cytotoxicity than the positive control, 5-fluorouracil (5-Fu), in SMMC-7721 cell line, with IC50 values of 15.85 and 12.06 ?M, whereas compound 30 exhibited more potent cytotoxicity than 5-Fu in NCI-H460 cell line, with an IC50 value of 5.19 ?M. In addition, this study suggests that compounds 11 and 30 from the wood of A. heterophyllus have anticancer potential via MAPK pathways.
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Tubastatin A/ACY-1215 improves cognition in Alzheimer's disease transgenic mice.
J. Alzheimers Dis.
PUBLISHED: 05-22-2014
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Histone deacetylase 6 (HDAC6) is currently being discussed as a promising therapeutic target for the treatment of Alzheimer's disease (AD). Mounting evidence indicates that increased HDAC6 expression may contribute to AD-associated neurodegeneration, although beneficial effects have also been identified. In the present study, we tested the potential of two selective HDAC6 inhibitors, tubastatin A and ACY-1215, to rescue cognitive deficits in a mouse model of AD. We found that both tubastatin A and ACY-1215 alleviated behavioral deficits, altered amyloid-? (A?) load, and reduced tau hyperphosphorylation in AD mice without obvious adverse effects. Our data suggested that tubastatin A and ACY-1215 not only promoted tubulin acetylation, but also reduced production and facilitated autophagic clearance of A? and hyperphosphorylated tau. Further, the decreased hyperphosphorylated tau and increased tubulin acetylation may account for the improved microtubule stability in AD mice after tubastatin A/ACY-1215 treatment. These preclinical results support the detrimental role of HDAC6 in AD, and offer prospective approaches for using tubastatin A/ACY-1215 as potential therapeutic strategy for AD.
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Experimental Mycobacterium tuberculosis infection in the Chinese tree shrew.
FEMS Microbiol. Lett.
PUBLISHED: 05-15-2014
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In recent years, the Chinese tree shrew has been considered to be a promising experimental animal for numerous diseases. Yet the susceptibility of Mycobacterium tuberculosis (MTB) in Chinese tree shrew is still unknown. We infected Chinese tree shrews with a high dose (2.5 × 10(6 ) CFU) or a low dose (2.5 × 10(3 ) CFU) of the H37Rv strain via the femoral vein to cause severe or mild disease. Disease severity was determined by clinical signs, pathologic changes and bacteria distribution in organs. Furthermore, among lung samples of the uninfected, mildly and seriously ill Chinese tree shrews, differentially expressed protein profiles were analyzed through iTRAQ and validated by qPCR. Tuberculous nodules, skin ulceration, pleural effusion and cerebellum necrosis could be observed in seriously ill animals. Regulation of the actin cytoskeleton was newly defined as a possible MTB-related pathway correlated with disease progression. This comprehensive analysis of the experimental infection and the depiction of the proteomics profiles in the Chinese tree shrew provide a foundation for the establishment of a new animal model of tuberculosis and provide a better understanding of the mechanism of tuberculosis.
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Bipolar radiofrequency ablation is useful for treating atrial fibrillation combined with heart valve diseases.
BMC Surg
PUBLISHED: 05-14-2014
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Atrial fibrillation (AF) is a common arrhymia, and it results in increased risk of thromboembolism and decreased cardiac function. In patients undergoing cardiac surgery, concomitant radiofrequency ablation to treat AF is effective in restoring sinus rhythm (SR). This study is an observational cohort study aimed to investigate the safety and efficacy of bipolar radiofrequency ablation (BRFA) for treating AF combined with heart valve diseases.
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[Histopathological changes in EV71-infected mouse model:a transmission electron microscopic study].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 04-19-2014
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To document ultrastructural changes of brain, spinal cord, skeletal muscle, jejunum and lung of EV71 infection mouse model, and to explore the myotropism and pathogenesis of EV71 in nervous system.
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Lowly pathogenic avian influenza (H9N2) infection in Plateau pika (Ochotona curzoniae), Qinghai Lake, China.
Vet. Microbiol.
PUBLISHED: 04-18-2014
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Avian influenza viruses (AIVs) are globally important contagions. Several domestic mammals can be infected with AIVs and may play important roles in the adaptation and transmission of these viruses in mammals, although the roles of wild mammals in the natural ecology of AIVs are not yet clear. Here, we performed a serological survey of apparently healthy Plateau pikas at Qinghai Lake in China to assess the prevalence of exposure to AIVs. Ninety-two of 293 (31%) of wild Plateau pikas possessed serum antibodies against a lowly pathogenic avian influenza (LPAI) H9N2 virus. Experimental inoculation of Plateau pikas with a LPAI H9N2 virus resulted in productive viral replication in respiratory tissues without prior adaptation. Our findings suggest that Plateau pikas represent a natural mammalian host to H9N2 AIVs and may play a role in the ongoing circulation of H9N2 viruses at Qinghai Lake in China. Surveillance for AIV infection in Plateau pika populations and other mammals that have close contact with the Plateau pikas should be considered.
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Distribution of enterovirus 71 RNA in inflammatory cells infiltrating different tissues in fatal cases of hand, foot, and mouth disease.
Arch. Virol.
PUBLISHED: 04-16-2014
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In previous studies of hand, foot, and mouth disease patients fatally infected with enterovirus 71 (EV71), the distribution of viral protein, but not the genome, was determined. To understand the pathogenesis of EV71, however, it is important to investigate the spread of the viral genome. There have been no pathological studies of in situ EV71 viral RNA in inflammatory cells infiltrating various tissues of fatal cases. We therefore first investigated the distribution and classification of inflammatory cells in various tissues and then performed in situ EV71 RNA hybridization in these tissues to better understand the pathogenesis of EV71 infection. EV71 RNA was found mainly in inflammatory cells infiltrating the central nervous system (CNS), intestines, lungs, and tonsils. Most EV71 RNA-positive inflammatory cells in the CNS were macrophages/microglia and neutrophils infiltrating the perivascular cuffing, microglial nodule, neuronophagia, and meninges. CD68+ macrophages and CD15+ neutrophils were diffusely distributed in tissues with severe pathological changes. This study demonstrates the presence of EV71 RNA in inflammatory cells infiltrating tissues in fatally infected patients. Our findings suggest that fatal EV71 infection with extensive infiltration of macrophages/microglia and neutrophils into the CNS results in severe neurological lesions.
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Fuzheng Huayu recipe alleviates hepatic fibrosis via inhibiting TNF-alpha induced hepatocyte apoptosis.
BMC Complement Altern Med
PUBLISHED: 04-08-2014
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What was the relationship of Fuzheng Huayu recipe (FZHY) inhibiting hepatocyte apoptosis and HSC activation at different stage of liver fibrosis? In order to answer this question, the study was carried out to dynamically observe FZHY's effect on hepatocyte apoptosis and HSC activation and further explored underling mechanism of FZHY against hepatocyte apoptosis.
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Induction of neutralizing antibodies to influenza A virus H7N9 by inactivated whole virus in mice and nonhuman primates.
Antiviral Res.
PUBLISHED: 04-04-2014
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We evaluated the immunogenicity of hemagglutinin (HA) in the context of inactivated H7N9/AH/1/13-PR8 whole-virion. At 4weeks after immunization with 15?g HA, mice produced hemagglutination inhibition (HI) titers of 1:192 and neutralizing antibodies of 1:317. Aluminum hydroxide (alum), or a booster immunization, or both increased HI to 1:768, 1:384, 1:896 and neutralizing antibodies to 1:1868, 1:2302, 1:10,000, respectively. Macaques generated HI of 1:190 or 1:360 and virus neutralizing titers of 1:280 or 1:658 at 3weeks after immunization with HA alone or with alum. Sera from immunized mice and macaques protected mice from infection of A/Anhui/1/2013 (H7N9), suggesting an H7N9 vaccine is immunologically feasible.
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Comparison of viral burden and disease progression in Chinese-origin rhesus macaques infected with common experimentally applied chimeric virus: SHIV-1157ipd3N4, SHIV-162P3, or SHIV-KB9.
J. Med. Primatol.
PUBLISHED: 03-27-2014
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Little is known about the comparative susceptibility and differential pathogenic characteristics of Chinese-origin rhesus macaques upon infection with the chimeric SHIVs most commonly applied in experimental research.
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Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma.
Mod. Pathol.
PUBLISHED: 03-14-2014
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Annexin A10 (ANXA10) is a member of the ANX family that is normally expressed in gastric mucosa. ANXA10 was recently observed to be upregulated in sessile serrated adenoma, a precursor to microsatellite-unstable colorectal cancer. We investigated the use of ANXA10 in diagnosing colorectal carcinoma. In an immunohistochemical analysis, the intensity and quantity of ANXA10, MUC5AC, MUC6 and CDX2 in 123 colorectal carcinomas were graded. We determined the molecular status of BRAF and KRAS mutations, as well as the microsatellite instability status and the CpG island methylator phenotype in all colorectal carcinomas, and subcategorized into four molecular subgroups according to the molecular derangements. Nuclear ANXA10 staining was present in 36 colorectal carcinomas, exhibiting a strong significant association with the BRAF mutation status (P<0.0001) and positive CpG island methylator phenotype (P<0.0001), and a borderline significant association with high levels of microsatellite instability (P=0.072). The ANXA10-positive colorectal carcinomas were frequently positive for MUC5AC and MUC6, and were associated with absent or reduced CDX2 expression (all P<0.0001). According to a classification and regression tree analysis, ANXA10 is a superior marker for the molecular subtyping of colorectal carcinomas and represents a specific marker for colorectal cancers of the serrated pathway. Our results indicated that ANXA10 expression is implicated in gastric programming in serrated-pathway-associated colorectal carcinoma. ANXA10-positive colorectal carcinoma is highly associated with the molecular features of the serrated neoplasia pathway.Modern Pathology advance online publication, 1 August 2014; doi:10.1038/modpathol.2014.96.
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The distribution of transplanted human mesenchymal stem cells in the CNS of young Macaca fascicularis.
Brain Res.
PUBLISHED: 03-14-2014
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Mesenchymal stem cell (MSC)-based therapies have generated much hope and promise as a potential source of cells for cell-based therapeutic strategies in pediatric degenerative diseases. However, the distribution and migratory routes of MSCs are unknown. Here, real-time PCR and microscopy were used to observe the migration and distribution of labeled human MSCs (hMSCs) transplanted into the striatum of young Macaca fascicularis. Moreover, the differentiation of hMSCs was also detected using immunofluorescence. We found that hMSCs were mainly located near the injection site in the brain and in the anterior brain after 2 weeks. After 4 weeks, the hMSCs had dispersed and could be detected in each brain slice and were more uniformly distributed than after 2 weeks. The hMSCs showed a preference for migration towards blood vessels, which may be one of the migratory routes used by hMSCs. Additionally, hMSCs could be observed to give rise to NeuN- and GFAP-positive cells. Transplanted hMSCs also increased the expression levels of N-cadherin in the host brain tissue, which may be one factor that drives the migration and differentiation of hMSCs after transplantation. These results provide preclinical evidence that MSC-based therapies may represent an efficacious alternative to more conventional treatment regimens for a variety of pediatric neurologic disorders.
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Antidepressant-like effects and mechanism of action of SYG in depression model in rats.
Neuro Endocrinol. Lett.
PUBLISHED: 03-09-2014
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The present study aimed to evaluate whether SYG, a Chinese herbal formula, could produce antidepressant-like effects in learned helplessness (LH) model and chronic mild stress (CMS) model in rats. The mechanism underlying the antidepressant-like action was investigated by exploring BDNF signaling way in the hippocampus.
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Prophylactic and therapeutic effect of AZT/3TC in RT-SHIV infected Chinese-origin rhesus macaques.
AIDS Res Ther
PUBLISHED: 02-26-2014
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The precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).
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IFN?-responsiveness of endothelial cells leads to efficient angiostasis in tumours involving down-regulation of Dll4.
J. Pathol.
PUBLISHED: 02-12-2014
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Although IFN? is regarded as a key cytokine in angiostatic response, our poor understanding of its effective cellular target drastically limits its clinical trials against angiogenesis-related disorders. Here, we investigated the effect of IFN? on endothelial cells (ECs) and possible molecular mechanisms in angiostasis. By employing Tie2(IFN?R) mice, in which IFN?R expression was reconstituted under the control of Tie2 promoter in IFN?R-deficient mice, we found that the response of ECs to IFN? was highly effective in inhibiting blood supply and retarding tumour growth. Interestingly, the expression of IFN?R on Tie2(-) cells did not inhibit, but promoted tumour growth in control wild-type mice. Mechanism studies showed that IFN? reacting on ECs down-regulated the delta-like ligand 4 (Dll4)/Notch signalling pathway. Accordingly, overexpression of Dll4 in human ECs diminished the effect of IFN? on ECs. This study demonstrates that the action of IFN? on ECs, but not other cells, is highly effective for tumour angiostasis, which involves down-regulating Dll4. It provides insights for EC-targeted angiostatic therapy in treating angiogenesis-associated disorders in the clinic.
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Free-space coherent optical communication with orbital angular, momentum multiplexing/demultiplexing using a hybrid 3D photonic integrated circuit.
Opt Express
PUBLISHED: 02-12-2014
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We demonstrate free-space space-division-multiplexing (SDM) with 15 orbital angular momentum (OAM) states using a three-dimensional (3D) photonic integrated circuit (PIC). The hybrid device consists of a silica planar lightwave circuit (PLC) coupled to a 3D waveguide circuit to multiplex/demultiplex OAM states. The low excess loss hybrid device is used in individual and two simultaneous OAM states multiplexing and demultiplexing link experiments with a 20 Gb/s, 1.67 b/s/Hz quadrature phase shift keyed (QPSK) signal, which shows error-free performance for 379,960 tested bits for all OAM states.
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Assessment of the pathogenesis of Streptococcus suis type 2 infection in piglets for understanding streptococcal toxic shock-like syndrome, meningitis, and sequelae.
Vet. Microbiol.
PUBLISHED: 02-08-2014
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Streptococcus suis type 2 (SS2) is an zoonotic pathogen that had caused outbreaks in 1998 and 2005 in China. It is still not very clear how the disease progresses into the streptococcal toxic shock-like syndrome (STSLS) or meningitis, as well as the sequelae from the survivals. The present study used piglets as infection model to systematically investigate the pathogenesis of the infection caused by the SS2 strain 05ZYH33. The infected piglets showed joint swelling, lameness, and crouch at beginning, then developed into septic-like shock syndrome (SLSS) or prostration syndrome, at last the survivals showed physical activity impairment. The morbidity and mortality were 100% (71% for SLSS, 29% for prostration syndrome) and 29%, respectively. The pigs exhibiting SLSS had deep invasive infections in tissues and organs, and displayed more severe bacteremia and cytokine secretion in the bloodstream and organs than pigs with prostration syndrome. Moreover, the polymorphisms in the toll-like receptor 1 (TLR1) and TLR2 genes varied between the pigs affected with SLSS and prostration syndrome. Several lines of evidence indicated that SS2 infection progression into SLSS or relatively lighter prostration syndrome in pigs is closely related to the degrees of bacteremia and cytokine storm, which may be inherently determined by the diversity of innate immunity-associated genes. Furthermore, brain lesions, such as venous thrombosis, may directly contribute to the sequelae in human cases, were identified in the pigs. These results might help us to further understand the pathogenesis of SS2 in humans.
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Rapid adaptation of avian H7N9 virus in pigs.
Virology
PUBLISHED: 01-20-2014
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How the H7N9 avian influenza virus gained the distinct ability to infect humans is unclear. Pigs are an important host in influenza virus ecology because they are susceptible to infection with both avian and human influenza viruses and are often involved in interspecies transmission. Here, we passaged one avian isolate and one human isolate in pigs to examine the mammalian host adaptation of the H7N9 virus. The avian virus replicated to a high titer after one passage, whereas the human isolate replicated poorly after three passages in pig lungs. Sequence analysis found nine substitutions in the HA, NA, M and NS segments of the avian isolate, which enhanced the binding affinity for human-type receptors. These results indicate that avian H7N9 influenza viruses can be easily adapted to pigs and that pigs may act as an important intermediate host for the reassortment and transmission of such novel viruses.
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A simian-human immunodeficiency virus carrying the rt gene from Chinese CRF01_AE strain of HIV is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivo.
Microbes Infect.
PUBLISHED: 01-16-2014
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Human immunodeficiency virus (HIV)-1 subtype CRF01_AE is one of the major HIV-1 subtypes that dominate the global epidemic. However, its drug resistance, associated mutations, and viral fitness have not been systemically studied, because available chimeric simian-HIVs (SHIVs) usually express the HIV-1 reverse transcriptase (rt) gene of subtype B HIV-1, which is different from subtype CRF01_AE HIV-1. In this study, a recombinant plasmid, pRT-SHIV/AE, was constructed to generate a chimeric RT-SHIV/AE by replacing the rt gene of simian immunodeficiency virus (SIVmac239) with the counterpart of Chinese HIV-1 subtype CRF01_AE. The infectivity, replication capacity, co-receptor tropism, drug sensitivity, and genetic stability of RT-SHIV/AE were characterized. The new chimeric RT-SHIV/AE effectively infected and replicated in human T cell line and rhesus peripheral blood mononuclear cells (rhPBMC). The rt gene of RT-SHIV/AE lacked the common mutation (T215I) associated with drug resistance. RT-SHIV-AE retained infectivity and immunogenicity, similar to that of its counterpart RT-SHIV/TC virus following intravenous inoculation in Chinese rhesus macaque. RT-SHIV-AE was more sensitive to nucleoside reverse transcriptase inhibitors (NRTIs) than the RT-SHIV/TC. RT-SHIV/AE was genetically stable in Chinese rhesus macaque. The new chimeric RT-SHIV/AE may be a valuable tool for evaluating the efficacy of the rt-based antiviral drugs against the subtype CRF01_AE HIV-1.
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Erythropoietin enhances mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia through Akt/eNOS signalling pathway.
Cell Biol. Int.
PUBLISHED: 01-16-2014
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Adaptation of cardiomyocytes to chronic hypoxia in cyanotic patients remains unclear. Mitochondrial biogenesis is enhanced in myocardium from cyanotic patients, which is possibly an adaptive response. Erythropoietin (EPO) in blood and its receptor (EPOR) on cardiomyocytes are upregulated by chronic hypoxia, suggesting that EPO-EPOR interaction is increased, which is inferred to positively regulate mitochondrial biogenesis through protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) signalling pathway. H9c2 cardiomyocytes were exposed to hypoxia (1% O(2)) for 1 week and treated with different doses of recombinant human erythropoietin (rhEPO). Mitochondrial number, mitochondrial DNA (mtDNA) copy number and peroxisome proliferator activated receptor gamma coactivator alpha (PGC-1?) mRNA expression increased in a dose-dependent manner induced by rhEPO. Akt and eNOS were significantly phosphorylated by rhEPO. Both blocking Akt with Wortmannin and silencing eNOS expression with shRNA plasmid decreased the mtDNA copy number and PGC-1? mRNA expression induced by rhEPO. Blocking Akt was associated with the decreased phosphorylation of Akt and eNOS. RNA interference led to a reduction in the total and phosphorylated proteins of eNOS. Thus EPO enhances mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia, at least partly through Akt/eNOS signalling, which might be an adaptive mechanism of cardiomyocytes associated with the increased EPO-EPOR interaction in patients with cyanotic congenital heart disease (CCHD).
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Histopathological features and distribution of EV71 antigens and SCARB2 in human fatal cases and a mouse model of enterovirus 71 infection.
Virus Res.
PUBLISHED: 01-12-2014
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Enterovirus 71 (EV71) is a neurotropic pathogen that causes hand, foot, and mouth disease. While infection is usually self-limiting, a minority of patients infected with EV71 develop severe neurological complications. In humans, EV71 has been reported to utilize the scavenger receptor class B, member 2 (SCARB2) as a receptor for infectious cellular entry. In this study, we define the pathological features of EV71-associated disease as well as the distribution of EV71 antigen and SCARB2 in human fatal cases and a mouse model. Histopathologically, human fatal cases showed severe central nervous system (CNS) changes, mainly in the brainstems, spinal cords, and thalamus. These patient further exhibited pulmonary edema and necrotic enteritis. Immunohistochemical analysis of human fatal cases demonstrated that EV71 antigen and SCARB2 were observed mainly in neurons, microglia cells and inflammatory cells in the CNS, and epithelial cells in the intestines. However, skeletal muscle tissue was negative for EV71 antigen. In a mouse model of EV71 infection, we observed massive necrotic myositis, different degrees of viral diseases in CNS, and extensive interstitial pneumonia. In mice, EV71 exhibits strong myotropism compared to the neurotropism seen in humans. EV71 antigen was detected in the spinal cord and brainstem of mice. However, there was no clear correlation between mouse SCARB2 and EV71 antigen distribution in the mouse model, consistent with previous results that SCARB2 functions as a receptor for EV71 in humans but not mice. The EV71-induced lesions seen in the mouse model resembled the pathological changes seen in human samples. These results increase our understanding of EV71 pathogenesis and will inform further work developing a mouse model for EV71 infection.
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Differential Regulation of Human Aortic Smooth Muscle Cell Proliferation by Monocyte-Derived Macrophages from Diabetic Patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Macrophage accumulation in the arterial wall and smooth muscle cell (SMC) proliferation are features of type 2 diabetes mellitus (DM) and its vascular complications. However, the effects of diabetic monocyte-derived macrophages on vascular SMC proliferation are not clearly understood. In the present study, we investigated the pro-proliferative effect of macrophages isolated from DM patients on vascular SMCs. Macrophage-conditioned media (MCM) were prepared from macrophages isolated from DM patients. DM-MCM treatment induced HASMC proliferation, decreased p21Cip1 and p27Kip1 expressions, and increased microRNA (miR)-17-5p and miR-221 expressions. Inhibition of either miR-17-5p or miR-221 inhibited DM-MCM-induced cell proliferation. Inhibition of miR-17-5p abolished DM-MCM-induced p21Cip1 down-regulation; and inhibition of miR-221 attenuated the DM-MCM-induced p27Kip1 down-regulation. Furthermore, blocking assays demonstrated that PDGF-CC in DM-MCM is the major mediators of cell proliferation in SMCs. In conclusion, our present data support the hypothesis that SMC proliferation stimulated by macrophages may play critical roles in vascular complications in DM patients and suggest a new mechanism by which arterial disease is accelerated in diabetes.
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Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Cervical cancer is the second leading cause of cancer morbidity and mortality for women around the world. Long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although downregulation of lncRNA GAS5 in several cancers has been studied, its role in cervical cancer remains unknown. The aim of this study is to investigate the expression, clinical significance and biological role in cervical cancer.
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Emergent endovascular vs. open surgery repair for ruptured abdominal aortic aneurysms: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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To systematically review studies comparing peri-operative mortality and length of hospital stay in patients with ruptured abdominal aortic aneurysms (rAAAs) who underwent endovascular aneurysm repair (EVAR) to patients who underwent open surgical repair (OSR).
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Early Effect of Essential Hypertension on the Left Ventricular Twist-Displacement Loop by Two-Dimensional Ultrasound Speckle Tracking Imaging.
Echocardiography
PUBLISHED: 12-05-2013
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To investigate two-dimensional (2D) ultrasound speckle tracking imaging (STI) in the evaluation of the early changes in the left ventricular (LV) twist-displacement loop in patients with hypertension (EH).
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Intranasal Immunization of Mice with Inactivated Virus and Mast Cell Activator C48/80 Elicits Protective Immunity against Influenza H1 but not H5.
Immunol. Invest.
PUBLISHED: 12-02-2013
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Vaccination represents the most economic and effective strategy of preventing influenza pandemics. We previously demonstrated that intranasal immunization of mice with recombinant hemagglutinin and the mast cell activator C48/80 elicited protective immunity against challenge with the 2009 pandemic H1N1 influenza in mice, demonstrating that the novel C48/80 mucosal adjuvant was safe and effective. The present study demonstrated that intranasal immunization with inactivated H1N1 virus and C48/80 elicited protective immunity against lethal challenge with homologous virus, however, when the immunogen was replaced with inactivated H5N1 virus protection was lost. These observations suggested that the adjuvant effects conferred by C48/80 were virus subtype specific and that its use as a broad-spectrum adjuvant for use in immunizations against all influenza viruses needs to be further analyzed.
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The application of on-pump beating-heart surgery for partial atrioventricular septal defect: a report of 87 cases.
Heart Surg Forum
PUBLISHED: 11-13-2013
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Partial atrioventricular septal defect (P-AVSD) is a common congenital heart disease. Because of the presence of left and right atrioventricular valve deformities and the shift in the atrioventricular node and cardiac conduction bundle, the surgical repair of P-AVSD is difficult. This study was performed to compare the effects on the coronary sinus septum in the left versus the right atrium during surgical treatment for P-AVSD and report our experiences regarding the application of on-pump beating heart surgery under mild hypothermia for patients with P-AVSD.
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An Animal Model of MERS Produced by Infection of Rhesus Macaques With MERS Coronavirus.
J. Infect. Dis.
PUBLISHED: 11-11-2013
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In 2012, a novel coronavirus (CoV) associated with severe respiratory disease, Middle East respiratory syndrome (MERS-CoV; previously known as human coronavirus-Erasmus Medical Center or hCoV-EMC), emerged in the Arabian Peninsula. To date, 114 human cases of MERS-CoV have been reported, with 54 fatalities. Animal models for MERS-CoV infection of humans are needed to elucidate MERS pathogenesis and to develop vaccines and antivirals. In this study, we developed rhesus macaques as a model for MERS-CoV using intratracheal inoculation. The infected monkeys showed clinical signs of disease, virus replication, histological lesions, and neutralizing antibody production, indicating that this monkey model is suitable for studies of MERS-CoV infection.
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Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions.
BMJ Open
PUBLISHED: 11-02-2013
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Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions.
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Antidepressant-like effects and memory enhancement of a herbal formula in mice exposed to chronic mild stress.
Neurosci Bull
PUBLISHED: 10-16-2013
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Shen Yuan Gan (SYG) is a Chinese herbal prescription composed of total saponins of Panax ginseng and total oligosaccharide esters of Polygala tenuifolia (2:1). Our previous studies have demonstrated that SYG has antidepressant-like effects in various mouse models of behavioral depression. The present study aimed to test whether SYG affected chronic mild stress (CMS)-induced depression and cognitive impairment in mice. We found that a 5-week CMS schedule induced significant degradation of the coat state, decreased sucrose intake in the sucrose-preference test, and increased the latency to feed in the noveltysuppressed feeding test. All of these CMS-induced changes were ameliorated by SYG (100 and 200 mg/kg) and fluoxetine (10 mg/kg). In addition, SYG restored the decreased monoamine neurotransmitter concentrations (serotonin, dopamine, norepinephrine and acetylcholine) induced by CMS in the prefrontal cortex. Interestingly, SYG ameliorated CMS-induced cognitive impairment in the step-through test, and increased the acetylcholine level in the prefrontal cortex. These results suggest that SYG has an antidepressant-like action and enhances cognition by modulating the serotonin, dopamine, norepinephrine, and acetylcholine levels in the prefrontal cortex.
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Antigenicity and transmissibility of a novel clade 2.3.2.1 avian influenza H5N1 virus.
J. Gen. Virol.
PUBLISHED: 09-28-2013
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A genetic variant of the H5N1 influenza virus, termed subclade 2.3.2.1, was first identified in Bulgaria in 2010 and has subsequently been found in Vietnam and Laos. Several cases of human infections with this virus have been identified. Thus, it is important to understand the antigenic properties and transmissibility of this variant. Our results showed that, although it is phylogenetically closely related to other previously characterized clade 2.3 viruses, this novel 2.3.2.1 variant exhibited distinct antigenic properties and showed little cross-reactivity to sera raised against other H5N1 viruses. Like other H5N1 viruses, this variant bound preferentially to avian-type receptors, but contained substitutions at positions 190 and 158 of the haemagglutinin (HA) protein that have been postulated to facilitate HA binding to human-type receptors and to enhance viral transmissibility among mammals, respectively. However, this virus did not appear to have acquired the capacity for airborne transmission between ferrets. These findings highlight the challenges in selecting vaccine candidates for H5N1 influenza because these viruses continue to evolve rapidly in the field. It is important to note that some variants have obtained mutations that may gain transmissibility between model animals, and close surveillance of H5N1 viruses in poultry is warranted.
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[Experimental study on co-culture of human fibroblasts on decellularized Achilles tendon].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 09-26-2013
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To investigate the preparation of decellularized Achilles tendons and the effect of co-culture of human fibroblasts on the scaffold so as to provide a scaffold for the tissue engineered ligament reconstruction.
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Identification and characterization of porcine kobuvirus variant isolated from suckling piglet in Gansu province, China.
Viruses
PUBLISHED: 09-19-2013
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Kobuviruses comprise three species, the Aichivirus A, Aichivirus B, and Aichivirus C (porcine kobuvirus). Porcine kobuvirus is endemic to pig farms and is not restricted geographically but, rather, is distributed worldwide. The complete genomic sequences of four porcine kobuvirus strains isolated during a diarrhea outbreak in piglets in the Gansu province of China were determined. Two of these strains exhibited variations relative to the traditional strains. The potential 3C/3D cleavage sites of the variant strains were Q/C, which differed from the Q/S in the traditional porcine kobuvirus genome. A 90-nucleotide deletion in the 2B protein and a single nucleotide insertion in the 3UTR were found in the variant strains. The VP1 regions of all four porcine kobuviruses in our study were highly variable (81%-86%). Ten common amino acid mutations were found specifically at certain positions within the VP1 region. Significant recombination sites were identified using SimPlot scans of whole genome sequences. Porcine kobuviruses were also detected in pig serum, indicating that the virus can escape the gastrointestinal tract and travel to the circulatory system. These findings suggest that mutations and recombination events may have contributed to the high level of genetic diversity of porcine kobuviruses and serve as a driving force in its evolution.
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Comparative analysis of curative effect of CT-guided stem cell transplantation and open surgical transplantation for sequelae of spinal cord injury.
J Transl Med
PUBLISHED: 09-15-2013
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This study compared the clinical efficacies, advantages and disadvantages of two transplantation approaches for treating spinal cord injury: open surgical exploration combined with local stem cell transplantation (referred to as open surgical transplantation) and local stem cell transplantation by CT-guided puncture (referred to as CT-guided transplantation).
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Novel Avian-Origin Human Influenza A(H7N9) Can Be Transmitted Between Ferrets via Respiratory Droplets.
J. Infect. Dis.
PUBLISHED: 08-29-2013
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The outbreak of human infections caused by novel avian-origin influenza A(H7N9) in China since March 2013 underscores the need to better understand the pathogenicity and transmissibility of these viruses in mammals. In a ferret model, the pathogenicity of influenza A(H7N9) was found to be less than that of an influenza A(H5N1) strain but comparable to that of 2009 pandemic influenza A(H1N1), based on the clinical signs, mortality, virus dissemination, and results of histopathologic analyses. Influenza A(H7N9) could replicate in the upper and lower respiratory tract, the heart, the liver, and the olfactory bulb. It is worth noting that influenza A(H7N9) exhibited a low level of transmission between ferrets via respiratory droplets. There were 4 mutations in the virus isolated from the contact ferret: D678Y in the gene encoding PB2, R157K in the gene encoding hemagglutinin (H3 numbering), I109T in the gene encoding nucleoprotein, and T10I in the gene encoding neuraminidase. These data emphasized that avian-origin influenza A(H7N9) can be transmitted between mammals, highlighting its potential for human-to-human transmissibility.
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Effects of quality assurance regulatory enforcement on performance of mammography systems: evidence from large-scale surveys in Taiwan.
AJR Am J Roentgenol
PUBLISHED: 07-26-2013
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The Standards for Medical Exposure Quality Assurance in mammography systems were enacted on July 1, 2008, in Taiwan. This study aimed to evaluate the trends in performance of mammography units before and after the regulation started on the basis of annual on-site surveys from 2008 to 2010.
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The determinants of activity and specificity in actinorhodin type II polyketide ketoreductase.
Chem. Biol.
PUBLISHED: 06-28-2013
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In the actinorhodin type II polyketide synthase, the first polyketide modification is a regiospecific C9-carbonyl reduction, catalyzed by the ketoreductase (actKR). Our previous studies identified the actKR 94-PGG-96 motif as a determinant of stereospecificity. The molecular basis for reduction regiospecificity is, however, not well understood. In this study, we examined the activities of 20 actKR mutants through a combination of kinetic studies, PKS reconstitution, and structural analyses. Residues have been identified that are necessary for substrate interaction, and these observations have suggested a structural model for this reaction. Polyketides dock at the KR surface and are steered into the enzyme pocket where C7-C12 cyclization is mediated by the KR before C9-ketoreduction can occur. These molecular features can potentially serve as engineering targets for the biosynthesis of novel, reduced polyketides.
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Complete preservation of the mitral valve apparatus during mitral valve replacement for rheumatic mitral regurgitation in patients with an enlarged left ventricular chamber.
Heart Surg Forum
PUBLISHED: 06-28-2013
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The merits of retaining the subvalvular apparatus during mitral valve replacement (MVR) for chronic mitral regurgitation have been demonstrated in clinical investigations. This study was to investigate the feasibility of total preservation of the leaflet and subvalvular apparatus at the native anatomic position during MVR in a rheumatic population with enlarged left ventricular chamber.
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Regulation of galectin-3-induced apoptosis of Jurkat cells by both O-glycans and N-glycans on CD45.
FEBS Lett.
PUBLISHED: 06-18-2013
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Galectin-3 has been reported to induce apoptosis of Jurkat cells through binding receptors such as CD45. CD45RABC is heavily O-glycosylated and N-glycosylated, while CD45RO is only N-glycosylated. In this study, no apoptosis induced by galectin-3 was detected in CD45RO-transfected cells, whereas apoptosis of CD45RABC-transfected cells was observed, implying that O-glycans on CD45 might play roles in galectin-3-induced apoptosis. O-Glycosylation inhibition assay further suggests the role of O-glycans on CD45 in regulation of galectin-3-induced apoptosis. We also found that deglycosylation at N327 of CD45RO resulted in increased binding to galectin-3 without affecting apoptosis, while deglycosylation at N36 or N109 of CD45RO enhanced galectin-3-induced apoptosis. These data demonstrate that galectin-3-induced apoptosis of Jurkat cells is regulated by both O-glycans and N-glycans on CD45.
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The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus.
Virol. J.
PUBLISHED: 06-18-2013
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The current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin H7N9 influenza virus.
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Interleukin-21 up-regulates interleukin-21R expression and interferon gamma production by CD8+ cells in SHIV-infected macaques.
Exp. Biol. Med. (Maywood)
PUBLISHED: 06-14-2013
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Interleukin-21 (IL-21) is produced primarily by CD4+ T cells and regulates immunity against human/simian immunodeficiency virus (HIV/SIV) infection. Activated CD8+ cells and their secreted interferon-gamma (IFN-?) are crucial for the control of acute HIV/SIV infection. However, whether IL-21 can regulate IFN-? production by CD8+ cells remains controversial. Rhesus macaques (RMs, n = 8) were infected with SHIV and the levels of plasma IL-21, IFN-? and the frequency of peripheral blood activated T cells were measured longitudinally. Following infection with SHIV, the levels of plasma IL-21 and IFN-? increased, peaked at 17 days postinfection and declined later. Furthermore, IL-21 induced IL-21 receptor (IL-21R) and IFN-?, perforin, but not granmyze B, expression in CD8+ cells from four selected SHIV-infected RMs. The regulatory effect of IL-21 on CD8+ cell function appeared to be associated with increased levels of STAT3, but not STAT5, phosphorylation in CD8+ cells from SHIV-infected RMs. In parallel, treatment with soluble IL-21R/Fc, an inhibitor of IL-21-induced activation of JAK1/3 and STAT3, abrogated IL-21-induced STAT3 activation and IFN-? production in CD8+ cells from SHIV-infected RMs in vitro. Our data indicated that IL-21 was a positive regulator of IFN-?-secreting CD8+ cells and increased the STAT3 phosphorylation, regulating T-cell immunity against acute SHIV infection in RMs. Our findings may provide a new basis for the development of immunotherapies for the control of SHIV/HIV infection.
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Trapping the dynamic acyl carrier protein in fatty acid biosynthesis.
Nature
PUBLISHED: 05-15-2013
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Acyl carrier protein (ACP) transports the growing fatty acid chain between enzymatic domains of fatty acid synthase (FAS) during biosynthesis. Because FAS enzymes operate on ACP-bound acyl groups, ACP must stabilize and transport the growing lipid chain. ACPs have a central role in transporting starting materials and intermediates throughout the fatty acid biosynthetic pathway. The transient nature of ACP-enzyme interactions impose major obstacles to obtaining high-resolution structural information about fatty acid biosynthesis, and a new strategy is required to study protein-protein interactions effectively. Here we describe the application of a mechanism-based probe that allows active site-selective covalent crosslinking of AcpP to FabA, the Escherichia coli ACP and fatty acid 3-hydroxyacyl-ACP dehydratase, respectively. We report the 1.9?Å crystal structure of the crosslinked AcpP-FabA complex as a homodimer in which AcpP exhibits two different conformations, representing probable snapshots of ACP in action: the 4-phosphopantetheine group of AcpP first binds an arginine-rich groove of FabA, then an AcpP helical conformational change locks AcpP and FabA in place. Residues at the interface of AcpP and FabA are identified and validated by solution nuclear magnetic resonance techniques, including chemical shift perturbations and residual dipolar coupling measurements. These not only support our interpretation of the crystal structures but also provide an animated view of ACP in action during fatty acid dehydration. These techniques, in combination with molecular dynamics simulations, show for the first time that FabA extrudes the sequestered acyl chain from the ACP binding pocket before dehydration by repositioning helix III. Extensive sequence conservation among carrier proteins suggests that the mechanistic insights gleaned from our studies may be broadly applicable to fatty acid, polyketide and non-ribosomal biosynthesis. Here the foundation is laid for defining the dynamic action of carrier-protein activity in primary and secondary metabolism, providing insight into pathways that can have major roles in the treatment of cancer, obesity and infectious disease.
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Efficacy and safety of pegylated interferon alfa-2b and ribavirin combination therapy versus pegylated interferon monotherapy in hemodialysis patients: a comparison of 2 sequentially treated cohorts.
Am. J. Kidney Dis.
PUBLISHED: 03-29-2013
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Pegylated interferon (peginterferon; interferon with an attached polyethylene glycol molecule) monotherapy is the recommended treatment for chronic hepatitis C virus (HCV) infection in hemodialysis patients. Limited data concerning peginterferon alfa-2b and ribavirin treatment in this population are available.
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Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71.
Int J Mol Sci
PUBLISHED: 03-07-2013
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Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. Presently, no vaccines or antiviral drugs have been clinically available to employ against EV71. In this study, we demonstrate that treatment with chebulagic acid reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC50 of 12.5 ?g/mL. The utilization of the chebulagic acid treatment on mice challenged with a lethal dose of enterovirus 71 was able to efficiently reduce mortality and relieve clinical symptoms through the inhibition of viral replication. Chebulagic acid may represent a potential therapeutic agent to control infections to enterovirus 71.
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Domestic cats and dogs are susceptible to H9N2 avian influenza virus.
Virus Res.
PUBLISHED: 02-26-2013
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Replication and transmission of avian influenza virus (AIV) in domestic dogs and cats may pose a risk to humans. The susceptibility of cats and dogs to H9N2 influenza virus was evaluated by intranasally or orally inoculating animals with an H9N2 influenza virus. Cats had recoverable virus in respiratory tissues and the olfactory bulb three days post-inoculation and shed H9N2 virus into nasal washes and pharyngeal swabs from day 2 through day 10 post-inoculation. Virus was recovered from respiratory tissues of dogs three days post-inoculation, but was not detected in nasal washes or pharyngeal swabs. While no virus shedding or replication was detected in cats or dogs following consumption of H9N2-infected chicks, one of two cats and one of two dogs seroconverted. Two of three naïve contact cats seroconverted following co-housing with cats that were intranasally inoculated with H9N2 virus, whereas none of the three naïve contact dogs seroconverted. Our results demonstrate that H9N2 AIV can infect domestic cats and dogs via the upper respiratory tract and indicate that cats are more susceptible than dogs to H9N2 AIV. These findings suggest that domestic dogs and cats may serve as host species contributing to the adaptation of H9N2 viruses in mammals.
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Comparison between calcitriol and calcitriol plus low-dose cinacalcet for the treatment of moderate to severe secondary hyperparathyroidism in chronic dialysis patients.
Nutrients
PUBLISHED: 02-16-2013
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Aim: Uremic hyperparathyroidism (UHPT) has been shown to contribute to the development and progression of chronic kidney disease-mineral bone disorder. UHPT is frequently observed in chronic dialysis patients, and patients with UHPT are associated with increased risk of all-cause and cardiovascular mortality. Cinacalcet is a novel agent that increases sensitivity to the calcium-sensing receptor and is approved for control of UHPT. Nevertheless, cinacalcet is costly and information regarding efficacy of low-dose cinacalcet on UHPT is limited. Methods: We conducted a retrospective study to evaluate treatment with either low-dose calcitriol combined with low-dose cinacalcet (25 mg) (d-cinacalcet) or calcitriol alone (VitD) in dialysis patients with moderate to severe UHPT. A total of 81 dialysis patients were enrolled (40 subjects in d-cinacalcet group and 41 subjects in VitD group). Demographic data including age, gender, duration on dialysis and biochemical data were reviewed and recorded. Results: At the end of the study, the intact parathyroid hormone (iPTH) levels of the d-cinacalcet group declined significantly (from 1166.0 ± 469.3 pg/mL to 679.8 ± 421.6 pg/mL, p < 0.0001), while there was no significant change in the VitD group. Significant decrease of serum calcium (Ca: 9.9 ± 0.6 mg/dL vs. 9.6 ± 0.8 mg/dL, p = 0.002), phosphorus (P: 5.9 ± 1.3 mg/dL vs. 4.9 ± 0.9 mg/dL, p < 0.0001) and calcium phosphate product (Ca × P: 58.7 ± 15.0 mg2/dL2 vs. 46.9 ± 8.9 mg2/dL2, p < 0.0001) were observed in the d-cinacalcet group. In addition, the subjects in the d-cinacalcet group had a greater proportion to achieve Kidney Disease Outcomes Quality Initiative (KDOQI)-recommended biochemical targets than the subjects in the VitD group (Ca: 48% vs. 24%; P: 78% vs. 32%; Ca × P: 85% vs. 37%; iPTH: 15% vs. 0%). Conclusions: We conclude that combination therapy of low-dose cinacalcet and calcitriol is more effective than calcitriol alone as a treatment for moderate and severe UHPT in chronic dialysis patients. Furthermore, this therapy is associated with improvement in hyperphosphatemia and hypercalcemia.
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Three unique Sendai virus antigenic peptides screened from nucleocapsid protein by overlapping peptide array.
J. Virol. Methods
PUBLISHED: 02-15-2013
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Sendai virus (SeV) is strictly monitored in laboratory rodents. Currently, complete virions have been used as antigens in SeV serological tests. However, the complexity of SeV virion antigen limits the accuracy of the diagnostic method. In the current study, complete SeV virion antigen was separated on SDS-PAGE and analyzed, with nucleocapsid protein (NP) showing predominant antigenicity. A peptide array containing overlapping 14-mer peptides covering the entire NP was developed. The array used SeV positive serum and resulted in four antigenic linear peptides being identified, which were located in the carboxyl-terminus of NP. The four peptides were coated on ELISA plates and tested with SeV positive and SeV negative sera, and the antigenicity of three peptides, NP413-428, NP473-490 and NP507-524, was confirmed. Mixture of the three peptides showed comparable sensitivity and better specificity in clinical rat sera ELISA tests compared with complete SeV virion antigen. In conclusion, the three peptides, NP413-428, NP473-490 and NP507-524, would be good candidates as linear antigens for SeV detection.
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Experimental infection of non-human primates with avian influenza virus (H9N2).
Arch. Virol.
PUBLISHED: 02-06-2013
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Several cases of humans infected with the H9N2 avian influenza virus (AIV) have been described since 1999; however, the infectivity and pathogenicity of H9N2 in humans is not well defined. A non-human primate model in rhesus macaques was developed to study H9N2 virus infections as a means of better understanding the pathogenesis and virulence of this virus, in addition to testing antiviral drugs. Rhesus macaques inoculated with H9N2 AIV presented with biphasic fever and viral pneumonia. H9N2 was recovered from nasal washes and pharyngeal samples up to days 7-9 postinfection, followed by an increase in HI (hemagglutination inhibition) antibody titers. Tissue tropism and immunohistochemistry indicated that H9N2 AIV replicated in the upper respiratory tract (turbinate, trachea, and bronchus) and in all lobes of the lung. Our data suggest that rhesus macaques are a suitable animal model to study H9N2 influenza virus infections, particularly in the context of viral evolution and pathogenicity.
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Probing the selectivity and protein·protein interactions of a nonreducing fungal polyketide synthase using mechanism-based crosslinkers.
Chem. Biol.
PUBLISHED: 02-03-2013
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Protein·protein interactions, which often involve interactions among an acyl carrier protein (ACP) and ACP partner enzymes, are important for coordinating polyketide biosynthesis. However, the nature of such interactions is not well understood, especially in the fungal nonreducing polyketide synthases (NR-PKSs) that biosynthesize toxic and pharmaceutically important polyketides. Here, we employ mechanism-based crosslinkers to successfully probe ACP and ketosynthase (KS) domain interactions in NR-PKSs. We found that crosslinking efficiency is closely correlated with the strength of ACP·KS interactions and that KS demonstrates strong starter unit selectivity. We further identified positively charged surface residues by KS mutagenesis, which mediates key interactions with the negatively charged ACP surface. Such complementary/matching contact pairs can serve as "adapter surfaces" for future efforts to generate new polyketides using NR-PKSs.
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The effect of PN-1, a Traditional Chinese Prescription, on the Learning and Memory in a Transgenic Mouse Model of Alzheimers Disease.
Evid Based Complement Alternat Med
PUBLISHED: 01-13-2013
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Traditional Chinese Medicine (TCM) is a complete medical system that has been practiced for more than 3000 years. Prescription number 1 (PN-1) consists of several Chinese medicines and is designed according to TCM theories to treat patients with neuropsychiatric disorders. The evidence of clinical practice suggests the benefit effects of PN-1 on cognitive deficits of dementia patients. We try to prove and explain this by using contemporary methodology and transgenic animal models of Alzheimers disease (AD). The behavioral studies were developed to evaluate the memory of transgenic animals after intragastric administration of PN-1 for 3 months. Amyloid beta-protein (A ? ) neuropathology was quantified using immunohistochemistry and ELISA. The western blotting was used to detect the levels of plasticity associated proteins. The safety of PN-1 on mice was also assessed through multiple parameters. Results showed that PN-1 could effectively relieve learning and memory impairment of transgenic animals. Possible mechanisms showed that PN-1 could significantly reduce plaque burden and A ? levels and boost synaptic plasticity. Our observations showed that PN-1 could improve learning and memory ability through multiple mechanisms without detectable side effects on mice. We propose that PN-1 is a promising alternative treatment for AD in the future.
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Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study.
Cytotherapy
PUBLISHED: 01-11-2013
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Pre-clinical evidence indicates that autologous bone marrow-derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function in patients with central nervous system disorders.
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Compromised NK cell-mediated antibody-dependent cellular cytotoxicity in chronic SIV/SHIV infection.
PLoS ONE
PUBLISHED: 01-10-2013
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Increasing evidence indicates that antibody-dependent cellular cytotoxicity (ADCC) contributes to the control of HIV/SIV infection. However, little is known about the ADCC function of natural killer (NK) cells in non-human primate model. Here we demonstrated that ADCC function of NK cells was significantly compromised in chronic SIV/SHIV infection, correlating closely with the expression of Fc?RIIIa receptor (CD16) on NK cells. CD32, another class of IgG Fc receptors, was identified on NK cells with higher expression in the infected macaques and the blockade of CD32 impacted the ability of NK cells to respond to antibody-coated target cells. The inhibition of matrix metalloproteases (MMPs), a group of enzymes normally involved in tissue/receptor remodeling, could restore NK cell-mediated ADCC with increased CD16 expression on macaque NK cells. These data offer a clearer understanding of NK cell-mediated ADCC in rhesus macaques, which will allow us to evaluate the ADCC repertoire arising from preclinical vaccination studies in non-human primates and inform us in the future design of effective HIV vaccination strategies.
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Repressive effect of primary virus replication on superinfection correlated with gut-derived central memory CD4(+) T cells in SHIV-infected Chinese rhesus macaques.
PLoS ONE
PUBLISHED: 01-01-2013
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A possible mechanism of susceptibility to superinfection with simian-human immunodeficiency virus (SHIV)-1157ipd3N4 was explored in twelve SHIVSF162P3-infected Chinese rhesus macaques. Based on the kinetics of viral replication for the second infecting virus following SHIV-1157ipd3N4 inoculation, the monkeys were divided into two groups: those relatively resistant to superinfection (SIR) and those relatively sensitive to superinfection (SIS). We found that superinfection-resistant macaques had high primary viremia, whereas superinfection-sensitive macaques had low primary viremia, suggesting that primary SHIVSF162P3 infection with a high viral-replication level would repress superinfection with a heterologous SHIV-1157ipd3N4. Although no correlation of protection against superinfection with virus-specific CD4(+) T cell or CD8(+) T cell immune responses from gut was observed prior to superinfection, superinfection susceptibility was strongly correlated with CD4(+) Tcm cells from gut both prior to the second infecting virus inoculation and on day 7 after superinfection, but not with CD4(+) Tem cells from gut or with CD4(+) Tcm cells from peripheral blood and lymph node. These results point to the important roles of gut-derived CD4(+) Tcm cells for the study of the mechanisms of protection against superinfection and the evaluation of the safety and efficacy of vaccines and therapies against acquired immune deficiency syndrome (AIDS).
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Lin28 mediates radiation resistance of breast cancer cells via regulation of caspase, H2A.X and Let-7 signaling.
PLoS ONE
PUBLISHED: 01-01-2013
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Resistance to radiation therapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to breast tumorigenesis; however, the relationship between Lin28 and radioresistance remains unknown. In this study, we investigated the association of Lin28 with radiation resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines. The results showed that the expression level of Lin28 was closely associated with resistance to radiation treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to radiation than MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which have low-level Lin28 expression. Transfection with Lin28 siRNA significantly led to an increase of sensitivity to radiation. By contrast, stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to radiation treatment. Stable expression of Lin28 also significantly inhibited radiation-induced apoptosis. Moreover, further studies have shown that caspases, H2A.X and Let-7 miRNA were the molecular targets of Lin28. Stable expression of Lin28 and treatment with radiation induced H2AX expression, while inhibited p21 and ?-H2A.X. Overexpression of Let-7 enhanced the sensitivities to radiation in breast cancer cells. Taken together, these results indicate that Lin28 might be one mechanism underlying radiation resistance, and Lin28 could be a potential target for overcoming radiation resistance in breast cancer.
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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.