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Find video protocols related to scientific articles indexed in Pubmed.
Generation of iPS Cells from Granulosa Cells.
Methods Mol. Biol.
PUBLISHED: 11-19-2014
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Various types of somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells. Somatic stem cells may generate iPS cells more efficiently than do differentiated cells. We show that granulosa cells exhibit characteristic of somatic stem cells and can be reprogrammed to iPS cells more efficiently or with few factors. Here, we describe generation of mouse and pig iPS cells from granulosa cells with high efficiency.
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Multimodality Imaging in Diagnosing Polypoidal Choroidal Vasculopathy.
Optom Vis Sci
PUBLISHED: 11-15-2014
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Report a case of polypoidal choroidal vasculopathy (PCV) and reveal its characteristics in multispectral imaging (MSI), a novel modality that examines individual retinal layers and enhances visualization of deep retinal structures.
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Mizoribine versus mycophenolate mofetil or intravenous cyclophosphamide for induction treatment of active lupus nephritis.
Chin. Med. J.
PUBLISHED: 11-11-2014
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Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Although there have been substantial improvements in LN treatment over the last decade, the outcome remains unoptimistic in a considerable percentage of patients. The aim of this study was to evaluate the efficacy and safety of mizoribine (MZR), a novel selective inhibitor of inosine monophosphate dehydrogenase, as induction treatment for active LN in comparison with mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC).
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Imaging diagnosis for left ventricular thrombosis in idiopathic hypereosinophilic syndrome: two case reports.
Medicine (Baltimore)
PUBLISHED: 10-03-2014
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Idiopathic hypereosinophilic syndrome (IHES) is a rare disease that is frequently associated with cardiac thrombosis and endocardial wall thickness. This case report describes 2 patients who had IHES associated with left ventricular (LV) thrombi. The patients' symptoms are atypical. Peripheral blood and bone marrow tests showed markedly elevated eosinophils. Electrocardiography showed ischemic changes in both patients. Negative computed tomography (CT) angiography excluded coronary artery stenosis. Transthoracic echocardiography (TTE), conventional multislice spiral CT, gemstone spectral CT, and cardiac magnetic resonance imaging were used to identify the LV intraluminal thrombus and endocardial thickening, and the diagnostic values of each imaging method were analyzed and compared. These patients were clinically diagnosed as "IHES, LV thrombosis, NYHA heart function classification I." Both patients received oral prednisone and warfarin therapy. At 5 month follow-up, TTE rechecks showed that the size of the LV thrombotic lesion was reduced in the first case but substantially increased in the second case.
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[Advance in studies on neuroprotective mechanism of Uncariae Ramulus Cum Uncis].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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The Uncariae Ramulus Cum Uncis is a commonly used traditional Chinese medicine. In recent years, many studies have revealed its prominent neuroprotection function. The active ingredients in Uncariae Ramulus Cum Uncis could protect the nervous system in a multi-path and multi-target manner. Uncariae Ramulus Cum Uncis shows the neuroprotective effect by resisting oxidation, scavenging free radicals, modulating neurotransmitters and their related receptors, regulating the inflammatory factors and their related pathways, attenuating neuron apoptosis, reducing intracellular Ca2+ overloads and mitigating neurodegeneration. In this paper, the authors summarized the advance in studies on neuroprotective mechanisms of Uncariae Ramulus Cum Uncis.
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Cigarette Smoke Attenuates the RIG-I-initiated Innate Antiviral Response to Influenza Infection in Two Murine Models.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 09-28-2014
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Cigarette smoke (CS) exposure increases the frequency and severity of respiratory tract infections. Despite this association, the mechanisms underlying the increased susceptibility to respiratory virus infection are poorly understood. Retinoic acid-inducible gene I (RIG-I) is an important regulator of in?uenza virus-induced expression of antiviral cytokines, mainly interferons (IFNs), which are necessary to clear viral infections. In this study, we compared the innate cytokine responses of two mouse CS exposure models following a challenge with influenza A virus (IAV): 1) exposure of the mice to cigarette smoke extract (CSE) intratracheally, and 2) exposure of the mice to CS in a whole-body exposure chamber. Both intratracheal CSE treatment and whole-body CS exposure caused antiviral immunosuppression in these mice, and both CS exposure methods inhibited RIG-I induction. CS attenuated influenza-induced antiviral IFNs and IP-10 expression in vivo. However, we did not find that CS inhibited induction of the proinflammatory cytokines IL-6 and TNF-?, whose expression was induced by IAV. Interestingly, IAV infection also increased toll-like receptor 3 (TLR3) expression in mouse lung, but CS exposure did not impact TLR3 induction in these mice. Together, the results support our previous finding in a human lung organ culture model that the suppression of RIG-I induction and antiviral cytokine responses by CS is likely important in the enhanced susceptibility of smokers to influenza infection in the lung.
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DNA-regulated silver nanoclusters for label-free ratiometric fluorescence detection of DNA.
Chem. Commun. (Camb.)
PUBLISHED: 09-24-2014
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Two kinds of DNA-regulated Ag nanoclusters were one-pot synthesized on an oligonucleotide, and delicately utilized in the design of a label-free ratiometric fluorescence strategy for DNA detection with simplicity and high sensitivity.
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The protective effect of ozone oxidative preconditioning against hypoxia/reoxygenation injury in rat kidney cells.
Ren Fail
PUBLISHED: 09-24-2014
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Abstract Ozone (O3) has been viewed as a novel treatment for different diseases in these years and oxidative stress and apoptosis play a key role in the pathogenesis of kidney diseases including renal ischemia and reperfusion (I/R). In the present study, we investigated the role of ozone oxidative preconditioning (OzoneOP) in attenuating oxidative stress and apoptosis in a hypoxia/reoxygenation (H/R) injury model using rat kidney cells. We induced H/R injury in kidney cells treated with or without OzoneOP. Oxidative stress parameters such as superoxide dismutase (SOD), malondialdehyde (MDA) and lactate dehydrogenase (LDH) were determined, as well as some apoptotic proteins. We observed that oxidative stress and apoptosis were increased in H/R group compared to OzoneOP group; however, these changes were significantly decreased by the treatment with OzoneOP. We concluded that OzoneOP can protect the kidney cells against H/R injury and its mechanism may be through the reduction of oxidative stress and apoptosis.
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Picroside II decreases the development of fibrosis induced by ischemia/reperfusion injury in rats.
Ren Fail
PUBLISHED: 09-24-2014
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In kidney transplantation, renal ischemia and reperfusion injury was one of the leading factors to the development of renal fibrosis, which was the main cause of graft loss. The fibrogenic changes were associated with the long term inflammation elicited by ischemia and reperfusion injury. In the present study, we investigated the role of the Picroside II, the main active constituents of the extract of picrorrhiza scrophulariiflora roots, in attenuating renal fibrosis in a renal ischemia and reperfusion injury model. We induced ischemia and reperfusion injury in kidneys treated with or without Picroside II. We observed that inflammation and tissue fibrosis were increased in ischemia and reperfusion injury group compared to Picroside II group, however, these changes were significantly decreased by the treatment with Picroside II. We concluded that Picroside II can protect the ischemic kidney against renal fibrosis and its mechanism may be through the inhibition of the long term inflammation.
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SPAG6 silencing inhibits the growth of the malignant myeloid cell lines SKM-1 and K562 via activating p53 and caspase activation-dependent apoptosis.
Int. J. Oncol.
PUBLISHED: 09-13-2014
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SPAG6, which is a novel cancer-testis antigen, is overexpressed in myeloid malignancies. Previously, SPAG6 was found in UPD (uniparental disomy) region of myeloid cell DNA from MDS patients and reported that SPAG6 may be a predictive marker of minimal residual disease in pediatric acute myeloid, but the biological role of SPAG6 in myeloid malignancies remains unclear. The present study was undertaken to determine the expression and functional significance of SPAG6 in malignant myeloid hematologic cell lines. A short hairpin RNA (shRNA) targeting SPAG6 was designed that could specifically inhibit SPAG6 expression at the mRNA and protein levels when introduced into the malignant myeloid hematologic cell lines SKM-1 and K562. The results from flow cytometry and CCK-8 assays showed that SPAG6 silencing inhibited the proliferation of SKM-1/K562 by inducing apoptosis. Furthermore, SPAG6 silencing resulted in activation of caspase-3, -9 and -8 and upregulated the mRNA and protein expression of p53 and PTEN. Then, we subcutaneously inoculated the monoclonal cells into NOD/SCID mice to establish xenograft models, and we found that the SPAG6-shRNA lentivirus dramatically inhibited tumor growth and increased apoptosis in vivo. These findings demonstrate that SPAG6 might have a role in malignant myeloid hematologic cell proliferation and apoptosis by regulating caspase proteins and p53, suggesting that SPAG6 may be a potential therapeutic target.
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Association of IL-18 promoter gene polymorphisms with rheumatoid arthritis: a meta-analysis.
Mol. Biol. Rep.
PUBLISHED: 09-06-2014
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Interleukin-18(IL-18) plays a potential pathological role in rheumatoid arthritis (RA). The conclusions of the published reports on the relationship between single-nucleotide polymorphisms -607C/A (rs1946518) and -137G/C (rs187238) located in the IL-18 gene promoter and RA risk remain controversial. This meta-analysis was performed to evaluate the association between IL-18 gene promoter (-607A/C and -137C/G) polymorphisms and RA using (1) allele, (2) codominant, (3) dominant, and (4) recessive models. Literature search was conducted up to January, 2013, in PubMed, EMBASE, Spring-link, Web of Science, Wanfang (Chinese) and China National Knowledge Infrastructure (CNKI). A total of 10 studies from eight articles involving 2,662 cases and 2,168 controls for -607A/C polymorphism and 9 studies from six articles involving 1,331 cases and 1,468 controls for -137C/G polymorphism were considered in the meta-analysis. For the relationship of IL-18 -607A/C polymorphism with RA risk, significant association was observed in allele model (OR = 0.778, 95 % CI = 0.633-0.955) and dominant model (OR = 0.618, 95 % CI = 0.466-0.819). However, no significant association could be observed between -137C/G polymorphism and RA risk under all genetic models (allele model: OR = 0.940, 95 % CI = 0.777-1.138; codominant model: OR = 1.079, 95 % CI = 0.574-2.029; dominant model: OR = 0.913, 95 % CI = 0.779-1.069; recessive model: OR = 1.133, 95 % CI = 0.586-2.190). In the subgroup analysis by ethnicity, significant result was also found in Asian populations but not found in Caucasian populations for the relationship of IL-18 -607A/C polymorphism with RA risk; while no obvious association was found between IL-18 -137C/G polymorphism and RA risk. This meta-analysis indicates that IL-18 -607A/C polymorphism in promoter region may be associated with RA risk.
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Identification of Klebsiella pneumoniae strains harboring inactive extended-spectrum beta-lactamase antibiotic-resistance genes.
Chin. Med. J.
PUBLISHED: 09-06-2014
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The extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae has increasingly become a major contributor to nosocomial infections and can exhibit multiple antibiotic resistance. Previous studies have focused on the resistance genes in ESBL-producing strains, and the resistance-associated genetic environment of non-ESBL-producing strains has been ignored until now. Here, we investigated the occurrence and characteristics of non-ESBL-producing K. pneumoniae, which potentially carries unexpressed resistance genes.
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Significantly enhanced dehydrogenation properties of calcium borohydride combined with urea.
Dalton Trans
PUBLISHED: 09-05-2014
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The interaction of [BH(x)]- and [NH(x)]-containing species gives rise to molecular hydrogen and the establishment of the B-N bond. Up to now, metal amides and ammonia are the commonly used [NH(x)] sources. Herein, urea, an organic carbonyl diamide, was used to react with Ca(BH4)2. A new type of complex hydride Ca(BH4)2·4CO(NH2)2 was synthesized with release of ca. 5.2 wt% hydrogen below 250 °C.
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Identifying direct miRNA-mRNA causal regulatory relationships in heterogeneous data.
J Biomed Inform
PUBLISHED: 08-30-2014
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Discovering the regulatory relationships between microRNAs (miRNAs) and mRNAs is an important problem that interests many biologists and medical researchers. A number of computational methods have been proposed to infer miRNA-mRNA regulatory relationships, and are mostly based on the statistical associations between miRNAs and mRNAs discovered in observational data. The miRNA-mRNA regulatory relationships identified by these methods can be both direct and indirect regulations. However, differentiating direct regulatory relationships from indirect ones is important for biologists in experimental designs. In this paper, we present a causal discovery based framework (called DirectTarget) to infer direct miRNA-mRNA causal regulatory relationships in heterogeneous data, including expression profiles of miRNAs and mRNAs, and miRNA target information. DirectTarget is applied to the Epithelial to Mesenchymal Transition (EMT) datasets. The validation by experimentally confirmed target databases suggests that the proposed method can effectively identify direct miRNA-mRNA regulatory relationships. To explore the upstream regulators of miRNA regulation, we further identify the causal feedforward patterns (CFFPs) of TF-miRNA-mRNA to provide insights into the miRNA regulation in EMT. DirectTarget has the potential to be applied to other datasets to elucidate the direct miRNA-mRNA causal regulatory relationships and to explore the regulatory patterns.
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KSR-based medium improves the generation of high-quality mouse iPS cells.
PLoS ONE
PUBLISHED: 08-29-2014
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Induced pluripotent stem (iPS) cells from somatic cells have great potential for regenerative medicine. The efficiency in generation of iPS cells has been significantly improved in recent years. However, the generation of high-quality iPS cells remains of high interest. Consistently, we demonstrate that knockout serum replacement (KSR)-based medium accelerates iPS cell induction and improves the quality of iPS cells, as confirmed by generation of chimeras and all iPS cell-derived offspring with germline transmission competency. Both alkaline phosphatase (AP) activity assay and expression of Nanog have been used to evaluate the efficiency of iPS cell induction and formation of ES/iPS cell colonies; however, appropriate expression of Nanog frequently indicates the quality of ES/iPS cells. Interestingly, whereas foetal bovine serum (FBS)-based media increase iPS cell colony formation, as revealed by AP activity, KSR-based media increase the frequency of iPS cell colony formation with Nanog expression. Furthermore, inhibition of MAPK/ERK by a specific inhibitor, PD0325901, in KSR- but not in FBS-based media significantly increases Nanog-GFP+ iPS cells. In contrast, addition of bFGF in KSR-based media decreases proportion of Nanog-GFP+ iPS cells. Remarkably, PD can rescue Nanog-GFP+ deficiency caused by bFGF. These data suggest that MAPK/ERK pathway influences high quality mouse iPS cells and that KSR- and PD-based media could enrich homogeneous authentic pluripotent stem cells.
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One-step synthesis of natural silk sericin-based microcapsules with bionic structures.
Macromol Rapid Commun
PUBLISHED: 08-28-2014
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Different techniques are being developed for fabricating microcapsules; it is still a challenge to fabricate them in an efficient and environment-friendly process. Here, a one-step green route to synthesize silk protein sericin-based microcapsules without any assistance of organic solvents is reported. By carefully changing the concentration of calcium ions accompanied with stirring, the morphology of the microcapsules can easily be regulated to form either discoidal, biconcave, cocoon-like, or tubular structures. The chelation of Ca(2+) and shearing force from agitation may induce the conformational transformation of sericin, which possibly results in the formation of microcapsules through the self-assembly of the protein subsequently. The as-prepared cocoon-like microcapsules exhibit pH-dependent stability. A potential application of microcapsules being fabricated from natural water-soluble silk protein sericin for controlled bioactive molecules loading and release system by a pH-triggered manner is quite feasible.
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The Sirius project.
J Synchrotron Radiat
PUBLISHED: 08-27-2014
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The lattice design and beam dynamics optimization for Sirius, a new low-emittance synchrotron light source presently under construction at the Brazilian Synchrotron Light Laboratory (LNLS) in Campinas, Brazil, is presented. The electron storage ring is based on a five-bend achromat (5BA) design achieving a bare lattice emittance of 0.28?nm?rad for a 3?GeV beam. The circumference of 518?m contains 20 achromatic straight sections of alternating 7?m and 6?m in length. An innovative approach is adopted to enhance the performance of the storage ring dipoles by combining low-field (0.58?T) magnets for the main beam deflection with a very short 2?T permanent-magnet superbend sandwiched in the center dipole. This superbend creates 12?keV critical photon energy dipole sources with modest total energy loss from dipoles. In addition it also creates a longitudinal dipole field gradient that reduces the emittance by about 10%. The optimized dynamic aperture allows for top-up operation with off-axis injection and the optimized energy acceptance allows for a total beam lifetime of around 11?h at nominal current with a third-harmonic cavity.
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Multicenter phase ii study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG).
J Hematol Oncol
PUBLISHED: 08-21-2014
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Improvement of current GVHD prophylactic therapies remains an important goal in the allo-HSCT. We have described a novel prophylaxis regimen in a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) initiated a phase II multicenter study.
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Primary epidural hemangiopericytoma in the sacrum: a rare case and literature review.
Tumour Biol.
PUBLISHED: 08-20-2014
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Hemangiopericytoma (HPC) is an uncommon highly vascular neoplasm that originated from Zimmerman's pericytes which surrounds the endothelial tissue. Primary epidural HPC of the sacrum is extremely rare. We reported an unusual case of primary epidural malignant HPC of the sacrum that invaded vertebral bone and caused rectum compression in a 57-year-old male for the first time. The patient presented progressive low back pain and ribbon-like stool over 3 months. The surgical intervention involved sacrectomy and en bloc resection of the tumor. We described the clinical, radiological, and histological features of this tumor and reviewed the literature.
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Circulating tumor cells are associated with bone metastasis of lung cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 08-16-2014
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Lung cancer (LC) is the leading cause of cancer mortality worldwide, predominantly due to the difficulty of early diagnosis and its high metastatic potential. Recently, increasing evidence suggests that circulating tumour cells (CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted interest in cancer metastasis detection and quantification. In present study, we collected blood samples from 67 patients with bone metastasis, and 30 patients without such metastasis, and searched for CTCs. Then the association of CTC numbers with bone metastasis and other clinico-pothological variants was analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the CTC number, there were significantly higher positivity of CTCs in the bone metastasis group than in the non-metastasis group. While the increase in CTC number was not significantly associated with any other clinicopathological factor, including age, gender, pathological type, intrapulmonary metastasis and lymph node metastasis, the CTC number in patients with positivity of the last above mentioned variants was obviously higher than in patients with negativity of the two variants. Taken together, the CTC number appears to be significantly associated with the bone metastasis from lung cancer.
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A meta-analysis of external fixator versus intramedullary nails for open tibial fracture fixation.
J Orthop Surg Res
PUBLISHED: 08-16-2014
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To compare the clinical outcomes of external fixator (EF) and intramedullary nails (IN) in the treatment of open tibial fractures.
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[Study on adjuvant effect of oral recombinant subunit vaccine formulated with chitosan against human enterovirus 71].
Bing Du Xue Bao
PUBLISHED: 08-15-2014
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To evaluate the adjuvant effect of recombinant enterovirus 71 (EV71) subunit vaccine formulated with chitosan, rabbits were orally immunized with recombinant VP1 (rVP1) or rVP1 mixed with chitosan adjuvant. Levels of virus-specific IgG and IgA antibodies in sera, mucosal wash buffer (intestine, nasal cavity, and lung), and feces were determined by indirect enzyme-linked immunosorbent assay (ELISA). The titers of neutralizing antibodies against EV71 were determined using cytopathic effect-based neutralizing assay, and levels of cytokines (IFN-gamma and IL-4) secreted from in vitro-cultured rabbit splenic lymphocytes under antigen stimulation were also determined by ELISA. Results showed that immunization with rVP1 alone could only induce low levels of serum IgG and mucosal IgA, while rVP1 combined with chitosan adjuvant were able to induce significantly higher levels of antibodies, rVP1 can only induce neutralizing antibodies when used in combination with chitosan. Levels of IFN-gamma and IL-4 in the group immunized with rVP1 plus chitosan were significantly higher than those in the group immunized with rVP1 only or those in the control groups. Our study lays the foundation for development of oral VP1 vaccine against EV71 infection.
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Decitabine, a new star in epigenetic therapy: the clinical application and biological mechanism in solid tumors.
Cancer Lett.
PUBLISHED: 08-14-2014
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Epigenetic alterations are strongly associated with cancer development and drug resistance. The use of the DNA methylation inhibitor decitabine (Dacogen®) has been approved in the treatment of hematological malignancies, and its clinical effects on solid tumors have gained attention. Here, we present a review of the molecular regulation mechanisms, clinical experiences and biological evaluation for novel decitabine-based therapies in solid tumors. We also discuss the following questions: What is the best administration schedule of decitabine in solid tumors? Is there tumor type specificity for decitabine-based epigenetic therapy? What are the biological function and mechanism of decitabine in suppressing tumor development? Is there a correlation between DNA demethylation and clinical response? Importantly, low-dose decitabine and combined therapy show significant improvement in solid tumor treatment. However, the correlation studies are preliminary, and key biomarkers for prognosis need further investigation.
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Pt@Au nanorods uniformly decorated on pyridyne cycloaddition graphene as a highly effective electrocatalyst for oxygen reduction.
ACS Appl Mater Interfaces
PUBLISHED: 08-13-2014
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Preparing metal-supported graphene nanocomposites is both interesting and challenging because of their well-defined morphologies and have potential application for oxygen reduction reaction (ORR). Here, we present an easy approach to synthesizing a novel hybrid material composed of Pt@Au nanorods (NRs) uniformly dispersed on the pyridyne cycloaddition of graphene (Pt@Au-PyNG), and the material serves as a high-performance catalyst for ORR. This hybrid electrocatalyst significantly decreases the use of Pt by using Pt dispersed on Au NRs and shows a markedly high activity toward ORR. The resulting Pt@Au-PyNG hybrid displayed comparable electrocatalytic activity and better stability than commercial Pt/C in alkaline solutions toward ORR. The hybrid effectively blocks CO formation to increase catalyst resistance to CO poisoning, thereby decreasing the amount of Pt needed. Free-energy diagrams for ORR on Pt@Au (111) through dissociative and associative mechanisms show that OH or O hydrogenation is the rate-limiting step based on DFT calculations.
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New open-framework cobalt sulfate-oxalates based on molecular and chain-like building blocks.
Dalton Trans
PUBLISHED: 08-12-2014
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Presented here are two novel open-framework cobalt sulfate-oxalates constructed from molecular and chain-like building blocks. The two compounds have different structures: an hcb-type layer with 20-ring windows and a mog-type framework with 12-ring channels. Amine molecules play dual roles in the two structures: as a chelating ligand and a charge-balancing agent.
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Direct sequencing of DNA pooling for screening highly informative SNPs in dairy cattle.
Yi Chuan
PUBLISHED: 07-31-2014
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In this study, 139 bovine single nuclear polymorphisms (SNPs) were firstly selected and then directly sequenced using DNA pooling. Based on the ratio of two signal peak values, 92 SNPs with the ratio over 1/2 were considered as potential highly informative markers. To further verify the reliability of screening system, 59 SNP markers were genotyped in 122 Holstein cattle using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) method. The results showed that 56 SNPs had a call rate higher than 85%. The minor allele frequency (MAF) of these 56 markers ranged from 0.27 to 0.5, with an average of 0.41; and in which 54 markers had a MAF over 0.3, covering 96.4% of this group of markers (54/56). Our findings indicate that direct sequencing of DNA pooling is a useful and efficient tool for identifying highly informative SNPs.
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Structural insights into the catalytic mechanism of Synechocystis magnesium protoporphyrin IX O-methyltransferase (ChlM).
J. Biol. Chem.
PUBLISHED: 07-30-2014
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Magnesium protoporphyrin IX O-methyltransferase (ChlM) catalyzes transfer of the methyl group from S-adenosylmethionine to the carboxyl group of the C13 propionate side chain of magnesium protoporphyrin IX. This reaction is the second committed step in chlorophyll biosynthesis from protoporphyrin IX. Here we report the crystal structures of ChlM from the cyanobacterium Synechocystis sp. PCC 6803 in complex with S-adenosylmethionine and S-adenosylhomocysteine at resolutions of 1.6 and 1.7 Å, respectively. The structures illustrate the molecular basis for cofactor and substrate binding and suggest that conformational changes of the two "arm" regions may modulate binding and release of substrates/products to and from the active site. Tyr-28 and His-139 were identified to play essential roles for methyl transfer reaction but are not indispensable for cofactor/substrate binding. Based on these structural and functional findings, a catalytic model is proposed.
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Role of miR-150 and Glycoprotein Non-metastatic Melanoma Protein B in Angiogenesis During Hyperoxia-induced Neonatal Lung Injury.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 07-24-2014
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Rationale. Glycoprotein non-metastatic melanoma protein B (GPNMB) has an important role in tissue repair and angiogenesis. Recently, we have demonstrated that hyperoxia-exposure down-regulates miR-150 expression and concurrent induction of its target gene, GPNMB, in neonatal rat lungs. Objective. This study aims to test the hypothesis that soluble GPNMB (sGPNMB) promotes angiogenesis in the hyperoxic neonatal lungs. Methods. Wild-type (WT) or miR-150 knock-out (KO) neonates, exposed to 95% O2 for 3, 6 and 10 days, were evaluated for lung phenotypes, GPNMB protein expression in the lungs and sGPNMB levels in the bronchoalveolar lavage. Angiogenic effects of sGPNMB were examined in vitro and in vivo. After a 6 day-exposure, similar analyses were performed in WT and miR-150 KO neonates during recovery at 7-21 days. Measurements and Main Results. miR-150 KO neonates displayed an increased capillary network, decreased inflammation and less alveolar damage compared to WT neonates after hyperoxia-exposure. The early induction of GPNMB and sGPNMB were found in miR-150 KO neonates. The recombinant GPNMB, which contained a soluble portion of GPNMB, promoted endothelial tube formation in vitro and enhanced angiogenesis in vivo. The increased capillaries in the hyperoxic lungs of miR-150 KO neonates appeared dysmorphic. They were abnormally enlarged in size and occasionally laid at sub-epithelial regions in the alveoli. However, the lung architecture returned to normal during recovery, suggesting that abnormal vascularity during hyperoxia does not affect postnatal lung development. Conclusions. GPNMB plays an important role in angiogenesis during hyperoxia-injury. Treatment with GPNMB may offer a novel therapeutic approach in reducing pathologic complications in bronchopulmonary dysplasia.
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Inferring condition-specific miRNA activity from matched miRNA and mRNA expression data.
Bioinformatics
PUBLISHED: 07-23-2014
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MicroRNAs (miRNAs) play crucial roles in complex cellular networks by binding to the messenger RNAs (mRNAs) of protein coding genes. It has been found that miRNA regulation is often condition-specific. A number of computational approaches have been developed to identify miRNA activity specific to a condition of interest using gene expression data. However, most of the methods only use the data in a single condition, and thus, the activity discovered may not be unique to the condition of interest. Additionally, these methods are based on statistical associations between the gene expression levels of miRNAs and mRNAs, so they may not be able to reveal real gene regulatory relationships, which are causal relationships.
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Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Impairment in Stroke Patients: A Meta-Analysis.
Mol. Neurobiol.
PUBLISHED: 07-18-2014
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Emerging evidence has shown that repetitive transcranial magnetic stimulation (rTMS) may significantly improve cognitive impairment in stroke patients, but individually published studies show inconclusive results. This meta-analysis aimed to derive a more precise estimation of the effects of rTMS on cognitive impairment in stroke patients based on studies published in peer-reviewed journals. A literature search of MEDLINE, Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, and three Chinese databases were conducted on articles published before April 30, 2014. Crude standardized mean difference (SMD) with 95 % confidence interval (CI) was calculated. Six clinical studies with a total of 132 stroke patients with cognitive impairment who underwent rTMS were included in this meta-analysis. The pooled results revealed that rTMS might significantly improve cognitive function in stroke patients (SMD?=?1.76, 95 % CI?=?0.43-3.10, P?
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MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome.
BMC Med Genomics
PUBLISHED: 07-16-2014
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Acute respiratory distress syndrome (ARDS) is characterized by pulmonary epithelial injury and extensive inflammation of the pulmonary parenchyma. Systematic analyses of microRNA (miRNA) and mRNA expression profiling in ARDS provide insights into understanding of molecular mechanisms of the pathogenesis of ARDS. The objective of this study was to identify miRNA and mRNA interactions in a rat model of ARDS by combining miRNA and mRNA microarray analyses.
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From miRNA regulation to miRNA-TF co-regulation: computational approaches and challenges.
Brief. Bioinformatics
PUBLISHED: 07-14-2014
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microRNAs (miRNAs) are important gene regulators. They control a wide range of biological processes and are involved in several types of cancers. Thus, exploring miRNA functions is important for diagnostics and therapeutics. To date, there are few feasible experimental techniques for discovering miRNA regulatory mechanisms. Alternatively, predictions of miRNA-mRNA regulatory relationships by computational methods have increasingly achieved promising results. Computational approaches are proving their ability as effective tools in reducing the number of biological experiments that must be conducted and to assist with the design of the experiments. In this review, we categorize and review different computational approaches to identify miRNA activities and functions, including the co-regulation of miRNAs and transcription factors. Our main focuses are on the recent approaches that use multiple data types for exploring miRNA functions. We discuss the remaining challenges in the evaluation and selection of models based on the results from a case study. Finally, we analyse the remaining challenges of each computational approach and suggest some future research directions.
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MEMS-BASED 3D CONFOCAL SCANNING MICROENDOSCOPE USING MEMS SCANNERS FOR BOTH LATERAL AND AXIAL SCAN.
Sens Actuators A Phys
PUBLISHED: 07-12-2014
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A fiber-optic 3D confocal scanning microendoscope employing MEMS scanners for both lateral and axial scan was designed and constructed. The MEMS 3D scan engine achieved a lateral scan range of over ± 26° with a 2D MEMS scanning micromirror and a depth scan of over 400 ?m with a 1D MEMS tunable microlens. The lateral resolution and axial resolution of this system were experimentally measured as 1.0 ?m and 7.0 ?m, respectively. 2D and 3D confocal reflectance images of micro-patterns, micro-particles, onion skins and acute rat brain tissue were obtained by this MEMS-based 3D confocal scanning microendoscope.
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miR-101 regulates expression of EZH2 and contributes to progression of and cisplatin resistance in epithelial ovarian cancer.
Tumour Biol.
PUBLISHED: 07-07-2014
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In order to determine the expression pattern of miR-101 in epithelial ovarian neoplasms and assess the functions and mechanism of miR-101 in tumorigenesis, we detected the expression of miR-101 and zeste homolog 2 (EZH2) in normal, benign, and malignant ovarian tissues and used miR-101 lentivirus infection to increase miR-101 expression in ovarian cancer cells and drug-resistant cancer cells. We found that miR-101 was underexpressed in epithelial ovarian cancer tissues, which significantly correlated with poor cell differentiation, advanced International Federation of Gynecology and Obstetrics (FIGO) stages, and ovarian cancer cell cisplatin resistance. miR-101 overexpression decreased the expression of EZH2, reduced proliferation and migration of ovarian cancer cells, and resensitized drug-resistant cancer cells to cisplatin-induced cytotoxicity, suggesting the important role miR-101 plays in ovarian cancer that may be associated with its function as a regulator targeting EZH2. Our findings show the potential of miR-101 as a diagnostic marker and new therapeutic target for patients with epithelial ovarian cancer.
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Genetic environment of ?-lactamase genes of extended-spectrum ?-lactamase-producing Klebsiella pneumoniae isolates from patients with lower respiratory tract infection in China.
Chin. Med. J.
PUBLISHED: 07-03-2014
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Extended-spectrum ?-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) is one of the most popular pathogens that cause refractory respiratory tract infection. The genetic environment, including insertion sequences and the types of promoter, plays a key role in exploration of the mechanism of prevalence and dismission of the ESBL-producing K. pneumoniae isolates. The aim of the investigation was to target analysis the genetic environment and promoter sequences of blaCTX-M, blaSHV and blaTEM, the most popular ?-lactamase genes harbored by ESBL-producing K. pneumoniae isolates.
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[Research progress in the study of brain microdialysis in glioma].
Yao Xue Xue Bao
PUBLISHED: 07-01-2014
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Glioma is the most common form of brain cancer. Despite recent advances in the treatment of solid tumors, there are few effective treatments for malignant gliomas due to its infiltrative nature. It has important significance to improve the treatment of glioma through in-depth understanding the intracerebral metabolic characteristics and pharmacokinetics of chemotherapeutics. Brain microdialysis (B-MD), an effective method to monitor central nervous system anticancer drug disposition, conditions of drugs through the blood-brain barrier, basic pathophysiologic metabolism, bioactive compounds and the changes of neurotransmitter in brain, provides the unique opportunity to allow the simultaneous determination of unbound concentrations of drugs in several tissues, and directly measure gliomas biochemistry continuously. B-MD has been able to monitor the change of brain drugs, metabolites and neurotransmitters, dynamic analysis of the drug concentration and pharmacological effect after administration, pharmacodynamic interaction between drugs, receptor mechanism of drug transport, as well as feedback information of internal environment. B-MD is expected to provide reference for clinical individual chemotherapy of glioma, but also provide powerful tools for the evaluation of new anticancer drugs in vivo. In this review, a comprehensive overview of B-MD for studies on glioma is elucidated with special emphasis on its application to neurochemistry and pharmacokinetic studies.
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Genetic deletion of calcium/calmodulin-dependent protein kinase kinase ß (CaMKK ß) or CaMK IV exacerbates stroke outcomes in ovariectomized (OVXed) female mice.
BMC Neurosci
PUBLISHED: 06-25-2014
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BackgroundStroke is the primary cause of long-term disability in the United States. Interestingly, mounting evidence has suggested potential sex differences in the response to stroke treatment in patients as, at least in part, distinct cell death programs may be triggered in females and males following stroke. The NIH has recognized that females are strikingly under-represented in pre-clinical trials. Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is a major kinase that is activated by elevated intracellular calcium. It has recently been suggested that CaMKK and CaMK IV, a downstream target molecule, are neuroprotective in stroke in males. In this study, we examined stroke outcomes in ovariectomized CaMKK ß and CaMK IV deficient females. Cell death/survival signaling and inflammatory responses were assessed.ResultsOur results demonstrated that CaMKK ß or CaMK IV KO exacerbated both ischemic injury and behavioral deficits in female mice. Genetic deletion of CaMKK ß or CaMK IV increased hemorrhagic transformation after stroke, and this was associated with both increased MMP9 activity and loss of the blood brain barrier (BBB) protein collagen IV. Transcriptional inactivation was observed in mice lacking either CaMKK ß or CaMK IV, as indicated by reduced levels of phosphorylated cAMP response element-binding protein (p-CREB) and B-cell lymphoma 2 (BCL-2) proteins. Finally, inhibiting this pathway exacerbated the inflammatory response to stroke as CaMKK ß or CaMK IV KO mice had increased levels of the pro-inflammatory serum cytokines tumor necrosis factor alpha (TNF¿) and interleukin 6 (IL-6) after stroke. This suggests that the CaMKK pathway is involved in the immune response to brain injury.ConclusionsInhibition of CaMKK signaling exacerbated stroke outcome and increased BBB impairment, transcriptional inactivation and inflammatory responses in females after stroke. Therefore, CaMKK signaling may be a potential target for stroke treatment in both males and females.
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Reflections on conducting evaluations for rural development interventions in China.
Eval Program Plann
PUBLISHED: 06-24-2014
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An appropriate evaluation methodology is critical in collecting valid data in complex development intervention contexts. This paper explores this issue by putting forward an appropriate evaluation methodology for development interventions in rural China. It draws on the experience of an impact evaluation of a sustainable agricultural biodiversity management project conducted in Hainan, China in 2010. The authors propose that evaluation be culturally responsive and the evaluation design be rooted in the particular cultural context where an evaluation is conducted. The appropriate use of the participatory rural appraisal (PRA) approach and methods helps generate data that are relevant and meaningful for evaluation purposes in rural China.
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Chimeric antigen receptor for adoptive immunotherapy of cancer: latest research and future prospects.
Mol. Cancer
PUBLISHED: 06-12-2014
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Chimeric antigen receptors (CARs) are recombinant receptors that combine the specificity of an antigen-specific antibody with the T-cell's activating functions. Initial clinical trials of genetically engineered CAR T cells have significantly raised the profile of T cell therapy, and great efforts have been made to improve this approach. In this review, we provide a structural overview of the development of CAR technology and highlight areas that require further refinement. We also discuss critical issues related to CAR therapy, including the optimization of CAR T cells, the route of administration, CAR toxicity and the blocking of inhibitory molecules.
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Zinc finger nuclease: a new approach for excising HIV-1 proviral DNA from infected human T cells.
Mol. Biol. Rep.
PUBLISHED: 06-12-2014
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A major reason that Acquired Immune Deficiency Syndrome (AIDS) cannot be completely cured is the human immunodeficiency virus 1 (HIV-1) provirus integrated into the human genome. Though existing therapies can inhibit replication of HIV-1, they cannot eradicate it. A molecular therapy gains popularity due to its specifically targeting to HIV-1 infected cells and effectively removing the HIV-1, regardless of viral genes being active or dormant. Now, we propose a new method which can excellently delete the HIV provirus from the infected human T cell genome. First, we designed zinc-finger nucleases (ZFNs) that target a sequence within the long terminal repeat (LTR) U3 region that is highly conserved in whole clade. Then, we screened out one pair of ZFN and named it as ZFN-U3. We discovered that ZFN-U3 can exactly target and eliminate the full-length HIV-1 proviral DNA after the infected human cell lines treated with it, and the frequency of its excision was about 30 % without cytotoxicity. These results prove that ZFN-U3 can efficiently excise integrated HIV-1 from the human genome in infected cells. This method to delete full length HIV-1 in human genome can therefore provide a novel approach to cure HIV-infected individuals in the future.
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Alterations of the human gut microbiome in liver cirrhosis.
Nature
PUBLISHED: 06-09-2014
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Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.
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D?galactose?induced mitochondrial DNA oxidative damage in the auditory cortex of rats.
Mol Med Rep
PUBLISHED: 06-02-2014
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Chronic administration of D?galactose (D?gal) is a useful method for establishing a model of natural aging in the auditory system. Previous studies have demonstrated that NADPH oxidases (NOXs) may be an important source of reactive oxygen species (ROS) in the peripheral auditory system (PAS) and cause an increase in mitochondrial DNA (mtDNA) common deletion (CD) levels in the PAS and central auditory system (CAS) of rats with D?gal?induced aging. However, the source of the ROS in the CAS and the mechanisms of age?related hearing loss (ARHL) have yet to be elucidated. In the present study, male Sprague Dawley rats were administered a daily injection of D?gal (150, 300 and 500 mg/kg, respectively) for eight weeks. All three doses of D?gal caused a significant increase in the expression of NOX2, 8?hydroxy?2?deoxyguanosine, a biomarker of DNA oxidative damage, and uncoupling protein 2, together with a decrease in the mitochondrial total antioxidant capabilities in the auditory cortex, as compared with the control rats (injected daily with the same volume of 0.9% saline for eight weeks). The levels of the mtDNA CD were also increased in the auditory cortex of the D?gal?induced aging rats. These findings suggest that both NOX? and mitochondria?associated ROS generation may contribute to mtDNA oxidative damage in the auditory cortex of the CAS of D?gal?induced aging rats. This study may provide novel insight into the development of ARHL.
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Hepatitis E virus infection in farmed rabbits and swine in the Eastern Chinese city Lianyungang: showing no potential interspecies transmission.
J. Med. Virol.
PUBLISHED: 05-30-2014
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Rabbit HEV isolated recently from farmed rabbits in China has been shown experimentally to be able to infect both cynomolgus macaques and pigs. The purpose of the present study was to investigate the extent to which cross-species transmission of rabbit HEV in farm settings is a significant factor in the spread of this zoonotic infection. Rabbit and swine feces were collected from the same area in Eastern China (Lianyungang City) and analyzed by RT-PCR. Partial genome sequencing of a 365?bp region of ORF2 from the HEV positive rabbit samples revealed that they had 92-99% sequence identity with rabbit strains (rbIM163-c1 and rbIM004) isolated from Inner Mongolia. Similarly, sequencing of a 765?bp region of ORF2 of HEV positive swine samples showed 96-98% sequence identity with genotype 4d isolates collected from patients in the Yantai and Nanjing regions of China. By contrast, the sequence identity between the rabbit and swine isolates was only 73-75%, with no molecular biological evidence of interspecies transmission having occurred. It is concluded that whilst interspecies infection with rabbit HEV can be achieved experimentally, in the field it is not a significant factor in zoonotic disease transmission at least in the area of China where this study was undertaken.
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RNA-Seq-based transcriptome analysis of methicillin-resistant Staphylococcus aureus biofilm inhibition by ursolic acid and resveratrol.
Sci Rep
PUBLISHED: 05-21-2014
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Bacterial biofilms are particularly problematic since they become resistant to most available antibiotics. Hence, novel potential antagonists to inhibit biofilm formation are urgent. Here the influences of two natural products, ursolic acid and resveratrol, on biofilm of the clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate were investigated using RNA-seq, and the differentially expressed genes were analyzed using Cuffdiff. The results showed that ursolic acid inhibition of biofilm formation may reduce amino acids metabolism and adhesins expression and resveratrol may disturb quorum sensing (QS) and the synthesis of surface proteins and capsular polysaccharides. In addition, the transcriptome analysis of resveratrol and the combination of resveratrol with vancomycin inhibition of established biofilm revealed that resveratrol would disturb the expression of genes related to QS, surface and secreted proteins, and capsular polysaccharides. These findings suggest that ursolic acid and resveratrol could be useful to be adjunct therapies for the treatment of MRSA biofilm-involved infections.
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Influence of blastocysts morphological score on pregnancy outcomes in frozen-thawed blastocyst transfers: a retrospective study of 741 cycles.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 05-13-2014
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The influence of inner cell mass (ICM) and trophectoderm (TE) score on pregnancy outcomes in frozen-thawed blastocyst transfer cycles was analyzed. A retrospective analysis of 741 cycles of frozen-thawed blastosysts transfer was performed. All cycles were divided into four groups based on the number and morphological score of blastocysts: S-ICM B/TE B group (n=91), the single blastocyst transfer of ICM B and TE B; D-ICM B/TE B group (n=579), double blastocysts transfer of ICM B/TE B; D-ICM B/TE C group (n=35), double blastocysts transfer of ICM B/TE C; and D-ICM C/TE B group (n=36), double blastocysts transfer of TE B/ICM C. The pregnancy outcomes were compared among the four groups. As compared with D-ICM B/TE C group, the clinical pregnancy rate, implantation rate and multiple pregnancy rate were increased in D-ICM B/TE B group (74.96% vs. 57.14%, 57.43% vs. 37.14%, and 48.62% vs. 25%, respectively, P<0.05 for all). Clinical pregnancy rate and implantation rate in D-ICM B/TE B group were also higher than in D-ICM C/TE B group (74.96% vs. 50%, and 57.43% vs. 33.33%, both P<0.05). Multivariable Logistic regression analysis indicated that ICM score was a better predictive parameter for clinical pregnancy (OR=3.05, CI 1.70-5.46, P<0.001), while the trophectoderm score was a better one for early abortion (OR=0.074, CI 0.03-0.19, P<0.001). Clinical pregnancy rate and multiple pregnancy rate in S-ICM B/TE B group were significantly lower than those in D-ICM B/TE B group (46.15% vs. 74.96%, and 2.38% vs. 48.62%, both P<0.05), but there was no significant difference in the implantation rate between the two groups. It was suggested that the higher score of ICM and TE may be indicative of the better pregnancy outcomes. The ICM score is a better predictor of clinical pregnancy than TE, while TE score is a better one in predicting early abortion. Single ICM B/TE B blastocyst transfer in frozen-thawed cycles can also get satisfactory pregnancy outcomes.
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Genome-wide association study for pigmentation traits in Chinese Holstein population.
Anim. Genet.
PUBLISHED: 05-13-2014
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With the Illumina BovineSNP50K BeadChip, we performed a genome-wide association study (GWAS) for two pigmentation traits in a Chinese Holstein population: proportion of black (PB) and teat colour (TC). A case-control design was used. Cases were the cows with PB <0.30 (n = 129) and TC <2 points (n = 140); controls were those with PB >0.90 (n = 58) and TC >4 points (n = 281). The RM test of roadtrips (version 1.2) was applied to detect SNPs for the two traits with 42 883 and 42 741 SNPs respectively. A total of nine and 12 genome-wide significant (P < 0.05) SNPs associated with PB and TC respectively were identified. Of these, two SNPs for PB were located within the KIT and IGFBP7 genes, and the other four SNPs were 23~212 kb away from the PDGFRA gene on BTA6; nine SNPs associated with TC were located within or 21~78.8 kb away from known genes on chromosomes 4, 11, 22, 23 and 24. By combing through our GWAS results and the biological functions of the genes, we suggest that the KIT, IGFBP7, PDGFRA, MITF, ING3 and WNT16 genes are promising candidates for PB and TC in Holstein cattle, providing a basis for further investigation on the genetic mechanism of pigmentation formation.
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The protective effects of Acanthus Ilicifolius alkaloid A and its derivatives on pro- and anti-inflammatory cytokines in rats with hepatic fibrosis.
Biotechnol. Appl. Biochem.
PUBLISHED: 04-21-2014
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This study was designed to investigate the protective effects of Ilicifolius Alkaloid A (4-hydroxy-2-benzoxazolone, HBOA) and its acetylated derivatives including 4-acetoxy-2-benzoxazolone (TC-2) and 3-acetyl-4-acetoxy-2-benzoxazolone (TC-3), on CCl4 -induced liver fibrosis in rats. Sprague-Dawley rats were given CCl4 twice per week for 8 weeks to induce liver fibrosis. Then they were treated with HBOA, TC-2 and TC-3 daily for 4 weeks, respectively. The serum indicators including total protein, albumin, globulin, hyaluronic acid and laminin were measured by commercial kits. The mRNA expression of adiponectin, peroxisome proliferator-activated receptor-gamma (PPAR-?), tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), transforming growth factor-?1 (TGF- ?1 ) and toll like receptor 4 (TLR4 ) were determined by RT-PCR. The proteins of adiponectin, TGF-?1 , ?-smooth muscle actin (?-SMA) and TLR4 were also detected by immunohistochemical assay. The results showed that HBOA, TC-2 and TC-3 significantly attenuated the fibrotic degree induced by CCl4 as evidenced by higher levels of total protein, albumin, adiponectin and PPAR-? which in turn decreased the proliferation of hepatic stellate cells. Moreover, those drugs markedly decreased the levels of hyaluronic acid, laminin, TNF-?, IL-6, TGF-?1 , ?-SMA and TLR4 . Our study indicates that HBOA, TC-2 and TC-3 have beneficial effects against liver fibrosis, and the mechanisms may be related to the inhibition of inflammatory response. This article is protected by copyright. All rights reserved.
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Probing interactions between human lung adenocarcinoma A549 cell and its aptamers at single-molecule resolution.
J. Mol. Recognit.
PUBLISHED: 03-26-2014
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Because cell-specific aptamers have high potential for biomedical applications, investigation of the interaction between cell and its aptamers may be of key importance for an improved understanding of biochemical processes. Herein, the interaction between human lung adenocarcinoma A549 cell and its four aptamers was explored using single-molecule force spectroscopy (SMFS). The values of the unbinding force varied from 117.1 to 171.0?pN at the loading rate of 1.8?×?10(5) ?pN/s. Based on the dependence of singe molecule force on the atomic force microscopy loading rate, the corresponding kinetic parameters were obtained. The results revealed two activation barriers and two transient states in the unbinding process of aptamer/cell interaction. More importantly, the binding sites on A549 cells with its four aptamers were defined to be different using SMFS and flow cytometry. This work demonstrated that SMFS can be used as a powerful tool for exploring the aptamer/cell binding behavior at the single-molecule level, and may provide valuable information for the design and application of aptamer probes.
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Controllable Synthesis of 3D Ni(OH)2 and NiO Nanowalls on Various Substrates for High-Performance Nanosensors.
Small
PUBLISHED: 03-26-2014
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Large-area and uniform three-dimensional (3D) ?-Ni(OH)2 and NiO nanowalls were synthesized on a variety of rigid and flexible substrates via a simple aqueous chemical deposition process. The ?-Ni(OH)2 nanowalls consist of single-crystal Ni(OH)2 nanosheets that were vertically grown on different substrates. The height, crystallinity, and morphology of the Ni(OH)2 nanowalls can be readily modified by adjusting the reaction time and concentration of the NiCl2 solution. The synthesis mechanism of the Ni(OH)2 nanowalls was determined through heterogeneous nucleation and subsequent oriented crystal growth. 3D NiO nanowalls were obtained by thermal decomposition of the Ni(OH)2 nanowalls at 400 °C in Ar atmosphere. Highly sensitive, selective gas sensors and electrochemical sensors based on these NiO nanowalls were developed. The chemiresistive gas sensors based on the NiO nanowalls grown on ceramic substrates exhibited an excellent performance with low detection limit for formaldehyde (8 ppb) and NO2 (15 ppb). The electrochemical sensor based on the NiO nanowalls grown on an FTO glass substrate had a superior selectivity to non-enzymatic glucose with a detection limit of 200 nm.
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Behavior of tetracycline and sulfamethazine with corresponding resistance genes from swine wastewater in pilot-scale constructed wetlands.
J. Hazard. Mater.
PUBLISHED: 03-26-2014
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Four pilot-scale constructed wetlands (free water surface, SF; horizontal subsurface flow, HSF; vertical subsurface flows with different water level, VSF-L and VSF-H) were operated to assess their ability to remove sulfamethazine (SMZ) and tetracycline (TC) from wastewaters, and to investigate the abundance level of corresponding resistance genes (sulI, sulII, tetM, tetW and tetO) in the CWs. The results indicated that CWs could significantly reduce the concentration of antibiotics in wastewater, and the mass removal rate range of SMZ and TC were respectively 11%-95% and 85%-95% in the four systems on the basis of hydraulic equilibrium; further relatively high removal rate was observed in VSF with low water level. Seasonal condition had a significant effect on SMZ removal in the CWs (especially SMZ in SF), but TC removal in VSFs were not considered to have statistically significant differences in winter and summer. At the end period, the relative abundances of target genes in the CWs showed obvious increases compared to initial levels, ranging from 2.98 × 10(-5) to 1.27 × 10(-1) for sul genes and 4.68 × 10(-6) to 1.54 × 10(-1) for tet genes after treatment, and those abundances showed close relation to both characteristic of wastewater and configuration of CWs.
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Knockdown of YAP1 inhibits the proliferation of osteosarcoma cells in vitro and in vivo.
Oncol. Rep.
PUBLISHED: 03-21-2014
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Yes-associated protein 1 (YAP1) is a candidate oncogene that is involved in tumorigenesis and progression of many malignant tumors. Recently, many studies have revealed that YAP1 is highly expressed in human osteosarcoma. To investigate the role of YAP1 in osteosarcoma tumorigenesis, the expression of YAP1 in the osteosarcoma cell lines (MG-63 and HOS) was knocked down by small hairpin RNA (shRNA), and the cell proliferation and colony formation assay showed that knockdown of YAP1 significantly suppressed the cell proliferation and colony formation of osteosarcoma cells. Subsequently, cell cycle distribution was analyzed by flow cytometry, and the results showed an accumulation of YAP1-knockdown cells in the G0/G1 phase, suggesting that YAP1 knockdown results in the arrest of cell cycle progression. Additionally, the knockdown of YAP1 also inhibited the tumorsphere formation in vitro and the growth of xenograft tumors in vivo. Therefore, these data suggest that YAP1 knockdown inhibits the proliferation of osteosarcoma cells. However, the mechanism of action was unclear. Further investigation showed that in the YAP1-knockdown MG-63 and HOS cells, the level of cylinD1 and c-myc expression, target genes of the Wnt signaling pathway and TOP-Flash reporter activity were all significantly decreased, which indicated that the inhibitory effect of YAP1 knockdown on osteosarcoma might be associated with the Wnt signaling pathway. Taken together, our results demonstrated that YAP1 is an important regulator of osteosarcoma tumorigenesis and knockdown of YAP1 would be a novel therapeutic strategy for osteosarcoma.
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Transcriptomic analysis of developmental features of Bombyx mori wing disc during metamorphosis.
BMC Genomics
PUBLISHED: 03-20-2014
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Wing discs of B. mori are transformed to pupal wings during the larva-to-pupa metamorphosis with dramatic morphological and structural changes. To understand these changes at a transcriptional level, RNA-seq of the wing discs from 6-day-old fifth instar larvae (L5D6), prepupae (PP) and pupae (P0) was performed.
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Ozone oxidative preconditioning inhibits renal fibrosis induced by ischemia and reperfusion injury in rats.
Exp Ther Med
PUBLISHED: 03-06-2014
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Ischemia and reperfusion injury (IRI) is a crucial contributor to the development of renal fibrosis. Ozone has been proposed as a novel medical therapy for various conditions, including organ IRI. The aim of this study was to investigate whether ozone oxidative preconditioning (OzoneOP) has a beneficial effect in preventing the development of renal fibrosis following IRI. Sprague Dawley rats were subjected to 45 min of ischemia followed by 8 weeks of reperfusion. Prior to surgery, rats in the OzoneOP group were treated with ozone and those in the IRI and Sham groups were untreated. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. To assess tissue fibrosis, Masson's trichrome staining was performed. Immunohistochemistry was also performed to determine the localization of ?-smooth muscle actin (?-SMA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to analyze the expression of transforming growth factor (TGF)-?1, ?-SMA and Smad7. The levels of BUN and Cr did not significantly differ between groups. Rats pretreated with ozone showed markedly less interstitial fibrosis than untreated rats following IRI. In addition, immunohistochemistry revealed that ?-SMA expression was attenuated in the OzoneOP group compared with the IRI group. RT-qPCR and western blot analysis showed that OzoneOP inhibited the IRI-induced increases in ?-SMA and TGF-?1 expression levels, and that the IRI-induced reduction in the expression of Smad7 was inhibited in the OzoneOP group. The results indicate that OzoneOP has beneficial effects on ischemic renal fibrosis. OzoneOP may exert its protective effects by a mechanism involving modulation of the TGF-?1/Smad7 pathway.
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MicroRNA-34a negatively regulates anesthesia-induced hippocampal apoptosis and memory impairment through FGFR1.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Mounting evidence has shown the toxic effects of anesthesia to neonatal hippocampus. We used an in vivo mouse model to explore the role of microRNA 34a (miR-34a) in regulating anesthesia-induced hippocampal neurotoxicity.
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Clinical significance of UGT1A1 gene polymorphisms on irinotecan-based regimens as the treatment in metastatic colorectal cancer.
Onco Targets Ther
PUBLISHED: 01-01-2014
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The primary aim of this research was to investigate the association between uridine diphosphate glucuronosyltransferase (UGT)1A1 gene polymorphisms and the toxicities of irinotecan-based regimens in Chinese patients with metastatic colorectal cancer.
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Experimental comparison of the reproductive outcomes and early development of the offspring of rats given five common types of drinking water.
PLoS ONE
PUBLISHED: 01-01-2014
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Tap water (unfiltered), filtered tap water and processed bottled water (purified water, artificial mineralized water, or natural water) are now the five most widely consumed types of drinking water in China. However, the constituents (organic chemicals and inorganic ingredients) of the five waters differ, which may cause them to have different long-term health effects on those who drink them, especially sensitive children. In order to determine which type of water among the five waters is the most beneficial regarding reproductive outcomes and the developmental behaviors of offspring, two generations of Sprague-Dawley rats were given these five waters separately, and their reproductive outcomes and the developmental behaviors of their offspring were observed and compared. The results showed that the unfiltered tap water group had the lowest values for the maternal gestation index (MGI) and offspring's learning and memory abilities (OLMA); the lowest offspring survival rate was found in the purified water group; and the highest OLMA were found in the filtered tap water group. Thus, the best reproductive and offspring early developmental outcomes were found in the group that drank filtered tap water, which had the lowest levels of pollutants and the richest minerals. Therefore, thoroughly removing toxic contaminants and retaining the beneficial minerals in drinking water may be important for both pregnant women and children, and the best way to treat water may be with granular activated carbon and ion exchange by copper zinc alloy.
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99mTc-3P4-RGD2 scintimammography in the assessment of breast lesions: comparative study with 99mTc-MIBI.
PLoS ONE
PUBLISHED: 01-01-2014
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To compare the potential application of (99m)Tc-3P-Arg-Gly-Asp ((99m)Tc-3P4-RGD2) scintimammography (SMM) and (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) SMM for the differentiation of malignant from benign breast lesions.
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Correlation between EGFR mutation status and response to first-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer.
Onco Targets Ther
PUBLISHED: 01-01-2014
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The purpose of this research was to investigate the relationship between epidermal growth factor receptor (EGFR) mutations and the response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).
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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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NOV-002, A Glutathione Disulfide Mimetic, Suppresses Tumor Cell Invasion and Metastasis.
J Carcinog Mutagen
PUBLISHED: 12-31-2013
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Metastasis is the major cause of death in cancer. Most therapies currently in the clinic aim to eradicate primary tumor, but do not have ideal effects on metastasis. The lack of effective therapy in metastasis prevention and treatment results in high mortality rate in cancer patients with advanced diseases. Here we report the oxidized glutathione small molecule compound NOV-002 reduces cancer cell invasion in vitro and metastasis in an animal model in combination with chemotherapy drug gemcitabine. NOV-002 regulates cell signaling pathways by suppressing ErbB2 and PI3K phosphorylation and subsequent inhibition of Akt and RhoA activation. Our results suggest that NOV-002 affects cell signaling pathways that are critical for invasion and metastasis and can potentially be effective in metastasis treatment in combination of other chemotherapies.
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[Effect of salidroside on apoptosis of bone marrow mesenchymal stem cells induced by ara-C].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 12-28-2013
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The purpose of this study was to investigate the effect of salidroside on human bone marrow mesenchymal stem cell (hBMMSC) apoptosis induced by cytarabine C(Ara-C) and its mechanism, hBMMSC were cultured in vitro and isolated by Fircoll density gradient centrifugation; cell surface antigens were measured by flow cytometry; the osteogenic and adipogenic differentiation of MSC was tested and evaluated by specific staining methods. The proliferation and apoptosis of cells exposed to Ara- C were detected by MTT and flow cytometry respectively. The expreiments were divided into 4 groups: control group, Ara-C group, salidroside group and Ara-C+salidroside group. The mRNA expression of BCL-2 and BAX was assayed by RT-PCR. The results showed that the adherent cells displayed spindle and fibroblast cell-like shape; the hBMMSC expressed CD44, CD71 and HLA-ABC, not expressed CD34, CD45 and HLA-DR; the hBMMSC successfully differentiated into osteogenic and adipogenic lineages, which showed mineralization with von Kossa staining. Furthermore, liquid vacuoles were detected by oil red O staining; Ara- C exhibited a less inhibitory effect on the proliferation of hBMMSC treated with slidroside. The apoptosis of hBMMSC treated with slidroside were significantly higher as compared with control group (P < 0.05); RT-PCR results demonstrated that the BCL-2 expression was significantly down regulated but BAX mRNA expressions was up-regulated in Ara- C group as compared with those in the control group. Salidroside significantly inhibited the apoptosis of MSC and reversed the mRNA expression of BCL-2 and BAX. It is concluded that salidroside can inhibit the apoptosis of hBMMSC induced by Ara-C, its mechanism may be related with the regulation of BCL-2/BAX expression.
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Design and static calibration of a six-dimensional force/torque sensor for minimally invasive surgery.
Minim Invasive Ther Allied Technol
PUBLISHED: 12-18-2013
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Abstract Introduction: The use of surgery robotics is getting more and more important worldwide. In the present study, we propose a novel small-size six-dimensional force/torque sensor with the structure of double cross beams. This technology can be applied in robotic tele-operation systems used in minimally invasive surgery (MIS) robotic systems. Material and methods: The proposed sensor is made of duralumin which totally meets the stiffness requirement. The output voltage of the sensor will alter with the deformation of the elastic body and strain gauges. The feasibility was discussed by finite element analysis (FEA) and the coupling coefficient matrix was established with dimension reduced according to FEA. In addition, we designed a calibration platform and completed static calibration for the sensor. The methods and principles of measurements and data analysis were provided. Results: The calibration curves and coupling coefficient matrix were acquired by using the least squares method (LSM). Conclusion: Experimental tests and calibration error analysis showed that the proposed sensor has high accuracy, appropriate range, and played a role in promoting the application of force feedback technology in MIS.
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State of polarization and propagation factor of a stochastic electromagnetic beam in a gradient-index fiber.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 12-11-2013
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With the help of a tensor method, we investigate the evolution properties of the state of polarization of an electromagnetic Gaussian Schell-model beam propagating through a gradient-index (GRIN) fiber. We find that the Stokes parameters and the polarization ellipse exhibit periodicity. The initial beam parameters affect the values of the Stokes parameters and the parameters of the polarization ellipse. Furthermore, based on the second-order moments of the Wigner distribution function, the explicit expression for the propagation factor (known as the M2 factor) in the GRIN fiber is derived. It is shown that the M2 factor remains invariant on propagation and is determined only by the initial beam parameters.
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Experimental demonstration of vortex phase-induced reduction in scintillation of a partially coherent beam.
Opt Lett
PUBLISHED: 12-11-2013
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We carry out experimental measurement of the scintillation index of a partially coherent beam-carrying vortex phase (i.e., Gaussian-Schell model vortex beam) propagating through thermally induced turbulence. It is demonstrated that a Gaussian-Schell model vortex beam has appreciably smaller scintillation than a Gaussian-Schell model beam, which will be useful in free-space optical communication.
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[A double antibody sandwich ELISA based assay for titration of severe fever with thrombocytopenia syndrome virus].
Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi
PUBLISHED: 12-11-2013
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To develop an assay for titration of severe fever with thrombocytopenia syndrome virus (SFTSV) based on double antibody sandwich ELISA.
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Aggregation kinetics of graphene oxides in aqueous solutions: experiments, mechanisms, and modeling.
Langmuir
PUBLISHED: 12-03-2013
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Although graphene oxide (GO) has been used in many applications to improve human life quality, its environmental fate and behavior are still largely unknown. In this work, a novel approach that combines experimental measurements and theoretical calculations was used to determine the aggregation kinetics of GO sheets in aqueous solutions under different chemistry conditions (e.g., cation valence and pH). Experimental data showed that both cation valence and pH showed significant effect on the aggregation of GO sheets. The measured critical coagulation concentrations were in good agreement with the predictions of the extended Schulze-Hardy rule. Ca(2+) and Mg(2+) were more effective than Na(+) in aggregating the GO sheets, which could be attributed to the cross-linking between GO sheets by the divalent cations through "bridging" the functional groups at the edges of the GO sheets. When solution pH increases, deprotonation of carboxylic groups was found to play a key role in increasing GO sheet stability and surface charge development. These results suggested that edge-to-edge and face-to-face interactions were the dominant modes of GO aggregation in the presence of divalent metal ions and H(+), respectively. A modified attachment efficiency (?) model was developed on the basis of the Maxwell approach with considerations of both primary and secondary minima. The model predictions matched the experimental measurements of the aggregation kinetics of GO sheets in aqueous solutions under all of the tested experimental conditions well.
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Optimal activation of carboxyl-superparamagnetic iron oxide nanoparticles bioconjugated with antibody using orthogonal array design.
J Nanosci Nanotechnol
PUBLISHED: 11-26-2013
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This study aims to bioconjugate anti-EMMPRIN monoclonal antibody on the surface of carboxyl-SPIO nanoparticles and to optimize the activated conditions of bioconjugation. Anti-EMMPRIN monoclonal antibody bioconjugated carboxyl-SPIO nanoparticles were performed through a coupling strategy of EDC and sulfo-NHS. The procedure was comprised of two steps by activation of carboxyl-SPIO nanoparticles and conjugation with monoclonal antibody. The optimal activated parameters of bioconjugation were evaluated by single factor design and orthogonal array design. SDS-PAGE analysis and Bradford assay was used for testing and verifying the efficiency of activated conditions obtained from orthogonal array. The results show that pH value, temperature and reaction time were important factors that influence bioconjugated efficiency. The activated parameters with pH value 6.2, temperature 25 degrees C and reaction time 30 min were obviously optimal for activation of carboxyl-SPIO nanoparticles and conjugation with monoclonal EMMPEIN antibody. This coupling strategy for anti-EMMPRIN mAb bioconjugated on SPIO nanoparticles was efficient, and may be further applied in the fields of medical or biological practices.
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SOX2 regulates apoptosis through MAP4K4-Survivin signaling pathway in human lung cancer cells.
Carcinogenesis
PUBLISHED: 11-14-2013
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Previous studies have implicated cancer stem cells in tumor recurrence and revealed that the stem cell gene SOX2 plays an important role in the tumor cell resistance to apoptosis. Nonetheless, the mechanism by which SOX2 regulates apoptosis signals remained undefined. Here, we demonstrated the surprising finding that silencing of the SOX2 gene effectively induces apoptosis via the activation of death receptor and mitochondrial signaling pathways in human non-small cell lung cancer cells. Unexpectedly, reverse transcription-PCR analysis suggested that downregulation of SOX2 leads to activation of MAP4K4, previously implicated in cell survival. Evaluation of the apoptotic pathways revealed an increased expression of key inducers of apoptosis, including tumor necrosis factor-? and p53, with concurrent attenuation of Survivin. Although p53 appeared dispensable for this pathway, the loss of Survivin in SOX2-deficient cells appeared critical for the observed MAP4K4 induced cell death. Rescue experiments revealed that SOX2-silencing-mediated killing was blocked by ectopic expression of Survivin, or by reduction of MAP4K4 expression. Clinically, expressions of Survivin and SOX2 were highly correlated with each other. The results reveal a key target of SOX2 expression and highlight the unexpected context-dependent role for MAP4K4, a pluripotent activator of several mitogen-activated protein kinase pathways, in regulating tumor cell survival.
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[Development of full-quantified HPLC fingerprint for quality evaluation of ophiopogonis radix of sichuan].
Zhong Yao Cai
PUBLISHED: 11-14-2013
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To establish HPLC fingerprint of Ophiopogonis Radix of Sichuan and simultaneously determine two homoisoflavonoids (methylophiopogonanones A and B).
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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