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Find video protocols related to scientific articles indexed in Pubmed.
Specific Gene Repression by CRISPRi System Transferred through Bacterial Conjugation.
ACS Synth Biol
PUBLISHED: 11-20-2014
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In microbial communities, bacterial populations are commonly controlled using indiscriminate, broad range antibiotics. There are few ways to target specific strains effectively without disrupting the entire microbiome and local environment. Here we use conjugation, a natural DNA horizontal transfer process among bacterial species, to deliver an engineered CRISPR interference (CRISPRi) system for targeting specific genes in recipient Escherichia coli cells. We show that delivery of the CRISPRi system is successful and can specifically repress a reporter gene in recipient cells, thereby establishing a new tool for gene regulation across bacterial cells and potentially for bacterial population control.
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Aromaticity Evaluations of Planar [6]Radialenes.
Org. Lett.
PUBLISHED: 11-20-2014
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The aromatic character of fused polycyclic systems varies with the nature of their annulated rings. Computed extra cyclic resonance energies (ECREs) reveal that the central six membered rings (6MRs) of the heterocyclic fused congeners 1-5 are "[6]radialene-like", but that the central 6MRs of triphenylene 9, coronene 10, and isocoronene 11 are "benzene-like." Comparisons with geometric (harmonic oscillator model of aromaticity, HOMA) and magnetic (nucleus independent chemical shifts, NICS) criteria illustrate the multifaceted nature of aromaticity in 1-11.
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Discovery and Characterization of the Tuberculosis Drug Lead Ecumicin.
Org. Lett.
PUBLISHED: 11-20-2014
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The new tuberculosis (TB) lead ecumicin (1), a cyclic tridecapeptide, was isolated from Nonomuraea sp. MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS(2). Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey's analysis.
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A quantitative evaluation of abdominal aorta aneurysm by CT images.
Technol Health Care
PUBLISHED: 11-20-2014
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An abdominal aorta aneurysm (AAA) is a disease that aortic vessel inflates abnormally. The aorta blows up continuously, which may lead to the rupture of the aorta. The mortality of rupturing the aorta is between 75 and 90% to properly treat this disease, we need to accurate measure about variation of AAA size. our team performed that AAA is reconstructed as three dimensional (3D) images by computer tomography (CT), and analyzed the elements of inflation through a geometric parameter measurement . Subjects (seven males) who undergo an AAA are enrolled for the analysis. The authors used CT images as a primary source, and obtained secondary CT images 12 months later.By means of these data, the authors constructed 3D images of AAA and performed examinations using a geometric analysis that calculates geometric parameter such as the tortuosity, diameter, saccular and so on based on volume, area of the segmented region of the CT slices that is set up by the centroids and 8 points around it. The result of the severity biomechanical factor shows increased AAA tortuosity ratio (4.9%), AAA diameter expansion ratio [cm/year] (6.8%), AAA total diameter ratio (4.7%), AAA saccular ratio (2.4%) than 12-month before. Through these results, We can plan to endovascular repair surgery to undergoing AAA patients and possible diagnosis estimation of AAA.
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Pharmacokinetic Properties of Two Erlotinib 150 mg Formulations with a Genetic Effect Evaluation in Healthy Korean Subjects.
Clin Drug Investig
PUBLISHED: 11-20-2014
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Erlotinib is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor that acts on the epidermal growth factor receptor and inhibits cell proliferation, growth, migration, invasion and survival. This study was performed for the subsequent marketing of a test erlotinib formulation in Korea. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy adult volunteers.
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Lifetime prevalence of and risk factors for suicidal ideation and suicide attempts in a korean community sample.
Psychiatry
PUBLISHED: 11-12-2014
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Our study evaluated the lifetime prevalence of and risk factors for suicidal ideation and suicide attempts in Jeollabuk-do Province, Korea.
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The 9-homocubyl cation rearrangement revisited.
Chem. Commun. (Camb.)
PUBLISHED: 11-06-2014
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Complexity of the potential energy surface of the 9-homocubyl cation is revealed by Born-Oppenheimer molecular dynamics simulations and high ab initio levels. The stereospecific automerizations observed experimentally involve bridged ions, which have either an aromatic or an anti-aromatic character. New pathways leading to more stable isomers are unveiled.
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Prevention of venous thromboembolism in cancer outpatients: guidance from the SSC of the ISTH: reply.
J. Thromb. Haemost.
PUBLISHED: 10-30-2014
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We appreciate the points raised by Dr. Oo in his correspondence regarding the ISTH SSC guidance statement on outpatient thromboprophylaxis in malignancy[1]. We note that he has made similar critiques in prior correspondence with some of us [2, 3]. We also note here that the purpose of an ISTH guidance statement (as opposed to a guideline) is to provide guidance to practicing physicians in areas where there is lack of sufficient evidence. This article is protected by copyright. All rights reserved.
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A synergistic effect of pretreatment on cell-wall structural changes in barley straw (Hordeum vulgare L.) for efficient bioethanol production.
J. Sci. Food Agric.
PUBLISHED: 10-25-2014
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Barley straw (Hordeum vulgare L.) is an attractive lignocellulosic material and is one of the most abundant renewable resources for fuel-ethanol production. Although it contains high cellulose and hemicellulose contents, it has several challenges and limitations in the process of converting barley straw (BS) to fuel-ethanol. High ash, silica, and lignin contents in barley straw make it an inferior feedstock for enzymatic hydrolysis. Pretreatment plays an important role for structural and compositional changes in increasing the efficiency of enzymatic hydrolysis and makes the whole process economically viable.
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Associations between Genetic Variants and Angiographic Characteristics in Patients with Coronary Artery Disease.
J. Atheroscler. Thromb.
PUBLISHED: 10-21-2014
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Aim: In this study, we investigated the genetic determinants of lesion characteristics and the severity of coronary artery disease (CAD) using a genome-wide association study (GWAS) and replication genotyping. Methods: The discovery set for GWAS consisted of 667 patients exhibiting angiographically diagnosed CAD with symptoms. For replication genotyping, 837 age- and sex-matched CAD patients were selected. Genetic determinants of lesion characteristics (diffuse vs. non-diffuse lesions), the number of diseased vessels (multi-vessel vs. single vessel disease) and the modified Duke score (high vs. low), which indicates the severity of CAD, were analyzed after adjusting for confounding factors. Results: Single nucleotide polymorphisms (SNPs) rs12917449, rs10152898 and rs231150 were associated with diffuse lesions, while rs1225006 and rs6745588 were associated with multi-vessel disease. However, on replication genotyping, no significant associations were found between any of these five SNPs and the lesion characteristics or CAD severity. In contrast, in the combined population of both the discovery and replication sets, genotypes rs125006 of CPNE4 and rs231150 of TRPS1 were found to be significantly associated with the modified Duke score. The addition of rs1225006 to conventional risk factors had significant incremental value in the model of the score. Conclusions: The associations between five SNPs identified using GWAS and angiographic characteristics were not significant in the current replication study. However, two variants, particularly rs1225006, were found to be associated with the severity of CAD in the combined set. These results indicate the potential clinical implication of these variants with respect to the risk of CAD.
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Astaxanthin lowers plasma TAG concentrations and increases hepatic antioxidant gene expression in diet-induced obesity mice.
Br. J. Nutr.
PUBLISHED: 10-20-2014
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Non-alcoholic fatty liver disease (NAFLD) is significantly associated with hyperlipidaemia and oxidative stress. We have previously reported that astaxanthin (ASTX), a xanthophyll carotenoid, lowers plasma total cholesterol and TAG concentrations in apoE knockout mice. To investigate whether ASTX supplementation can prevent the development of NAFLD in obesity, male C57BL/6J mice (n 8 per group) were fed a high-fat diet (35 %, w/w) supplemented with 0, 0·003, 0·01 or 0·03 % of ASTX (w/w) for 12 weeks. The 0·03 % ASTX-supplemented group, but not the other groups, exhibited a significant decrease in plasma TAG concentrations, suggesting that ASTX at a 0·03 % supplementation dosage exerts a hypotriacylglycerolaemic effect. Although there was an increase in the mRNA expression of fatty acid synthase and diglyceride acyltransferase 2, the mRNA levels of acyl-CoA oxidase 1, a critical enzyme in peroxisomal fatty acid ?-oxidation, exhibited an increase in the 0·03 % ASTX-supplemented group. There was a decrease in plasma alanine transaminase (ALT) and aspartate transaminase (AST) concentrations in the 0·03 % ASTX-supplemented group. There was a significant increase in the hepatic mRNA expression of nuclear factor erythroid 2-related factor 2 and its downstream genes, which are critical for endogenous antioxidant mechanism, in the 0·03 % ASTX-supplemented group. Furthermore, there was a significant decrease in the mRNA abundance of IL-6 in the primary splenocytes isolated from the 0·03 % ASTX-supplemented group upon lipopolysaccharide (LPS) stimulation when compared with that in the splenocytes isolated from the control group. In conclusion, ASTX supplementation lowered the plasma concentrations of TAG, ALT and AST, increased the hepatic expression of endogenous antioxidant genes, and rendered splenocytes less sensitive to LPS stimulation. Therefore, ASTX may prevent obesity-associated metabolic disturbances and inflammation.
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Genomic Alterations in the RB Pathway Indicate Prognostic Outcomes of Early-Stage Lung Adenocarcinoma.
Clin. Cancer Res.
PUBLISHED: 10-09-2014
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Purpose: To better understand the complete genomic architecture of lung adenocarcinoma (LA). Experimental Design: We used array experiments to determine copy number variations and sequenced the complete exomes of the 247 LA tumor samples along with matched normal cells obtained from the same patients. Fully annotated clinical data were also available, providing an unprecedented opportunity to assess the impact of genomic alterations on clinical outcomes. Results: We discovered that genomic alternations in the RB pathway are associated with significantly shorter disease-free survival in early-stage LA patients. This association was also observed in our independent validation cohort. The current treatment guidelines for early-stage LA patients recommend follow-up without adjuvant therapy after complete resection, except for high-risk patients. However, our findings raise the interesting possibility that additional clinical interventions might provide medical benefits to early-stage LA patients with genomic alterations in the RB pathway. When examining the association between genomic mutation and histological subtype, we uncovered the characteristic genomic signatures of various histological subtypes. Notably, the solid and the micropapillary subtypes demonstrated great diversity in the mutated genes, while the mucinous subtype exhibited the most unique landscape. This suggests that a more tailored therapeutic approach should be used to treat LA patients. Conclusion: Our analysis of the genomic and clinical data for 247 LAs should help provide a more comprehensive genomic portrait of LA, define molecular signatures of LA subtypes, and lead to the discovery of useful prognostic markers that could be used in personalized treatments for early-stage LA patients.
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The regulation of the oxidative phase of the pentose phosphate pathway: New answers to old problems.
IUBMB Life
PUBLISHED: 09-22-2014
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There is a paradox in the oxidizing phase of the phosphate pentose pathway that has not yet been solved. The flow through the pathway is reduced in basal conditions; however, it must rise notably when a NADPH supplement is required. The paradox consists of the strong inhibition that the NADPH exerts on the both dehydrogenases of the pathway, especially on the regulating enzyme glucose-6-phosphate dehydrogenase (G6PD). Theoretically, in anabolic situations, the increase of gene expression of G6PD and 6-phosphogluconate dehydrogenase can induce a rise in the production of NADPH, which would cause the immediate inhibition of the enzyme and a drastic flow reduction. However, increasing the flow through oxidative phase of the pentose phosphate pathway (OPPP) has been experimentally demonstrated in many physiological states. However, this situation will be resolved if the NADPH metabolized or otherwise sufficient NADPH is sequestered to relax the inhibition of the dehydrogenases of OPPP and to maintain high ratio of NADPH/NADP(+) needed to ensure the reducing environment of the cell cytoplasm and the contribution of NADPH for anabolic processes. In 1974, the presence of a protein capable of reversing the inhibition of G6PD by NADPH was detected; however, to date, this paradox remains undisclosed. This review deals with the possibility that such reverting action might be similar to the activity of a protein named HSCARG, which is responsible for the abduction of NADPH, thus keeping a portion of the coenzyme away from the catalytic action and, simultaneously, the immune response through the NF-?B (nuclear factor kappa light-chain enhancer of activated B cells) system. The model has many similarities with the hypothesis proposed some 40 years back on the reversion of G6PD inhibition by NADPH. © 2014 IUBMB Life, 2014.
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Exploratory investigation of genetic associations with basal cell carcinoma risk: genome-wide association study in Jeju Island, Korea.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-18-2014
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Little is known about the genetic associations with Basal cell carcinoma (BCC) risk in non-Caucasian populations, in which BCC is rare, as in Korea. We here conducted a pilot genome-wide association study (GWAS) in 12 patients and 48 standard controls.
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Relationship Between Oxidative Stress and Bone Mass in Obesity and Effects of Berry Supplementation on Bone Remodeling in Obese Male Mice: An Exploratory Study.
J Med Food
PUBLISHED: 09-09-2014
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Abstract Berry consumption can prevent bone loss. However, the effects of different berries with distinct anthocyanin composition have not been thoroughly examined. The present study compared the effects of blueberry, blackberry, and black currant on bone health using a mouse model of diet-induced obesity. To investigate the effect of different berry supplements against a high-fat (HF) diet in vivo, 40 HF diet-induced obese (DIO) C57BL mice were assigned into four groups and fed a HF diet (35% w/w) with or without berry supplementation for 12 weeks (n=10). We measured adipose tissue mass (epididymal and retroperitoneal), plasma antioxidant, bone-related biomarkers, femur bone mineral density (BMD), and bone mineral content (proximal and distal). Adipose masses were negatively correlated with proximal BMD, but positively associated with plasma superoxide dismutase (SOD) concentrations (P<.001). Berry supplementation did not change the plasma ferric reducing antioxidant power, SOD, and insulin-like growth factor-1. However, the black currant group exhibited greater plasma alkaline phosphatase compared with the control group (P<.05). BMD in the distal epiphysis was significantly different between the blueberry and blackberry group (P<.05). However, berry supplementation did not affect bone mass compared with control. The present study demonstrates a negative relationship between fat mass and bone mass. In addition, our findings suggest that the anthocyanin composition of berries will affect bone turnover, warranting further research to investigate the underlying mechanisms.
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Ameliorative effects of Monascus pilosus-fermented black soybean (Glycine max L. Merrill) on high-fat diet-induced obesity.
J Med Food
PUBLISHED: 08-12-2014
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Abstract The purpose of this study was to examine the antiobesity effects of Monascus pilosus-fermented black soybean (F-BS) in C57BL/6 mice with high-fat diet (HFD)-induced obesity. F-BS (oral, 0.5 and 1.0?g/kg per body weight, twice per day) ameliorated obesity by reducing body and liver weight increases, and regulating blood glucose and cholesterol levels in C57BL/6 mice fed a control or HFD with oral administration of F-BS for 12 weeks. F-BS suppressed the growth of epididymal, retroperitoneal, and perirenal fat pads by preventing increases in the adipocyte size. Moreover, the levels of blood glucose, total cholesterol, and leptin were significantly lowered by F-BS administration in a dose-dependent manner. These results indicated that F-BS is a beneficial food supplement for preventing obesity, controlling blood glucose, and lowering cholesterol. Future research strategies should address the mechanisms that selectively regulate obesity, including hyperglycemia and hypercholesterolemia.
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Therapeutic Implications of Protein Disulfide Isomerase Inhibition in Thrombotic Disease.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 08-07-2014
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The study of thrombus formation has increasingly applied in vivo tools such as genetically modified mice and intravital microscopy to the evaluation of molecular and cellular mechanisms of thrombosis. Among several unexpected findings of this approach was the discovery that protein disulfide isomerase serves an essential role in thrombus formation at sites of vascular injury. The observation that the commonly ingested quercetin flavonoid, quercetin-3-rutinoside, inhibits protein disulfide isomerase and blocks thrombus formation in preclinical studies has set the stage for clinical trials using protein disulfide isomerase antagonists as antithrombotics. Although the mechanisms by which protein disulfide isomerase facilitates platelet activation and fibrin formation have yet to be elucidated, protein disulfide isomerase antagonists are currently being developed as antithrombotics. This review will consider what is known about the role of protein disulfide isomerase in platelet accumulation and fibrin generation with a focus on pharmacological strategies for blocking protein disulfide isomerase activity in the context of thrombus formation. Potential indications and clinical trial design for testing the efficacy of protein disulfide isomerase inhibition to reduce the incidence of thrombosis will be considered.
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Estrogenic Endocrine-Disrupting Chemicals Modulate the Production of Inflammatory Mediators and Cell Viability of Lipopolysaccharide-Stimulated Macrophages.
Inflammation
PUBLISHED: 07-26-2014
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Estrogenic endocrine-disrupting chemicals (EDCs) are exogenous substances that act as competitive inhibitors of estrogen in the endocrine system. By disrupting the endocrine system, EDCs can cause severe disabilities and diseases, including cancers and altered sexual development. Although the influence of these molecules in the endocrine system is evident, the effects of EDCs on the immune system as well as their cytotoxicity have been poorly examined. Therefore, we selected 21 EDCs that are commonly found in Korean ecosystems, such as surface waters and effluents, and studied their immunologic effects by comparing nitric oxide (NO) production and cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (RAW cells), a macrophage cell line. Among the EDCs tested, fenitrothion (FTH) inhibited the messenger RNA (mRNA) expression of inducible NO synthase (iNOS), resulting in reduced NO production, while treatment with andostenedione (AD), diethyl phthalate, di-n-butyl phthalate (DBP), estriol, or molinate decreased production of NO in an iNOS-independent fashion. In contrast, benzo(a)pyrene (B(a)P) increased the production of NO in RAW cells. In addition, AD, DBP, or FTH inhibited the mRNA expression of tumor necrosis factor alpha or interleukin-1 beta. Treatment with 17-?-ethynylestradiol, 17-?-estradiol, 4-n-butyl phenol, or alachlor induced apoptosis of RAW cells, while dicyclohexyl phthalate and B(a)P caused cell death in an apoptosis-independent manner. These data suggest that EDCs can influence the immune response to pathogens by modulating the functions of macrophages.
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The validities and efficiencies of korean ADHD rating scale and korean child behavior checklist for screening children with ADHD in the community.
Psychiatry Investig
PUBLISHED: 07-21-2014
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The purpose of this study is to examine the validity of primary screening tools for attention deficit hyperactivity disorder (ADHD) in a community-based sample of children using the Korean version of the Child Behavior Checklist (K-CBCL) and the Korean version of the ADHD Rating Scale (K-ARS).
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Crystallization and preliminary X-ray analysis of the C-terminal fragment of Ski7 from Saccharomyces cerevisiae.
Acta Crystallogr F Struct Biol Commun
PUBLISHED: 07-04-2014
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Ski7 (superkiller protein 7) plays a critical role in the mRNA surveillance pathway. The C-terminal fragment of Ski7 (residues 520-747) from Saccharomyces cerevisiae was heterologously expressed in Escherichia coli and purified to homogeneity. It was successfully crystallized and preliminary X-ray data were collected to 2.0?Å resolution using synchrotron radiation. The crystal belonged to a trigonal space group, either P3121 or P3221, with unit-cell parameters a = b = 73.5, c = 83.6?Å. The asymmetric unit contains one molecule of the C-terminal fragment of Ski7 with a corresponding crystal volume per protein mass (VM) of 2.61?Å(3)?Da(-1) and a solvent content of 52.8% by volume. The merging R factor is 6.6%. Structure determination by MAD phasing is under way.
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LSM14A inhibits porcine reproductive and respiratory syndrome virus (PRRSV) replication by activating IFN-? signaling pathway in Marc-145.
Mol. Cell. Biochem.
PUBLISHED: 07-03-2014
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Porcine reproductive and respiratory syndrome virus (PRRSV) is considered as a significant contributor to porcine reproductive and respiratory syndrome, one of the most economically important diseases for the pig industry worldwide. Emerging evidence indicates that pattern recognition receptors play key roles in recognizing pathogen-associated molecular patterns. In the present study, we investigated the effects of a novel pattern recognition receptor LSM14A in regulating PRRSV replication. Results in Marc-145 cells and porcine alveolar macrophages (PAMs) indicated that overexpression of porcine LSM14A effectively inhibited the replication of PRRSV, and knockdown of LSM14A by siRNA enhanced the replication of PRRSV. Mechanistically, LSM14A up-regulated the activities of IFN-? and ISRE promoters, enhanced the production of IFN-?, RIG-I, and ISGs, and inhibited the production of the inflammatory cytokines of TNF-? and IL-6 mRNA. Additionally, the expression pattern of LSM14A during the infection of PRRSV in Tongcheng and Large White pigs was suppressed by the PRRSV challenge. Taken together, our results suggest that LSM14A is an important PRR that inhibits PPRSV replication by inducing IFN-? signaling and restraining inflammatory responses. Furthermore, the down-regulation of LSM14A by PRRSV might represent an important mechanism by which PRRSV invades the host. Our study sheds light on the possibility of developing a new strategy to control this disease.
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Postprandial glucose-lowering effects of fermented red ginseng in subjects with impaired fasting glucose or type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial.
BMC Complement Altern Med
PUBLISHED: 07-03-2014
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Red ginseng is prepared by steaming raw ginseng, a process believed to increase the pharmacological efficacy. Further bioconversion of red ginseng through fermentation is known to increase its intestinal absorption and bioactivity, and bioconversion diminishes the toxicity of red ginseng's metabolite. This study was conducted to investigate the effects of daily supplementation with fermented red ginseng (FRG) on glycemic status in subjects with impaired fasting glucose or type 2 diabetes.
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Docosahexaenoic acid-induced apoptosis is mediated by activation of mitogen-activated protein kinases in human cancer cells.
BMC Cancer
PUBLISHED: 06-30-2014
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The role of omega-3 polyunsaturated fatty acids (?3-PUFAs) in cancer prevention has been demonstrated; however, the exact molecular mechanisms underlying the anticancer activity of ?3-PUFAs are not fully understood. Here, we investigated the relationship between the anticancer action of a specific ?3-PUFA docosahexaenoic acid (DHA), and the conventional mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK) and p38 whose dysregulation has been implicated in human cancers.
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Fractionated Gamma Knife Radiosurgery for Benign Perioptic Tumors: Outcomes of 38 Patients in a Single Institute.
Brain Tumor Res Treat
PUBLISHED: 06-10-2014
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This study was performed to evaluate the efficacy and safety of fractionated Gamma Knife radiosurgery (GKRS) for perioptic lesions.
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Gamma knife radiosurgery of the symptomatic brain stem cavernous angioma with low marginal dose.
Clin Neurol Neurosurg
PUBLISHED: 05-28-2014
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To analyze the outcome of gamma knife radiosurgery (GKS) using low marginal dose for the symptomatic brain stem cavernous angioma (BSCA).
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Unconventional approaches to the prevention of cancer associated thrombosis.
Thromb. Res.
PUBLISHED: 05-28-2014
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A number of strategies are currently under investigation to prevent venous thromboembolic events in cancer cohorts. Based on the efficacy of low molecular weight heparin in the treatment of thrombosis in cancer patients, a number of clinical studies have focused on evaluating the efficacy the low molecular weight heparins in the primary thromboprophylaxis setting. Further refinements in defining which cancer cohorts are at greatest risk of suffering thromboembolic events are under investigation such as clinical-laboratory risk scores and biomarkers such as tissue factor-bearing microparticles. However, alternative approaches to primary thromboprophylaxis beyond standard anticoagulants are also being evaluated in the clinic such anti-platelet agents, statins to reduce circulating tissue factor, and scheduled monitoring for venous thromboembolic events without pharmacologic thromboprophylaxis. In addition, clinical studies are underway to evaluate the antithrombotic efficacy of targeting extracellular protein disulfide isomerase with oral flavonoids (e.g. quercetin and isoquercetin). Emerging data regarding these unconventional approaches in the prevention of thromboembolic events in cancer patients is reviewed.
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Pharmacokinetics of a new orally soluble film formulation of sildenafil administered without water.
Int J Clin Pharmacol Ther
PUBLISHED: 05-20-2014
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To compare the pharmacokinetic profiles and to assess bioequivalence of a newly developed orally soluble film formulation of sildenafil, taken without water, with those of a conventional formulation of sildenafil.
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Clinical features and treatment outcome of chordoid meningiomas in a single institute.
J Korean Neurosurg Soc
PUBLISHED: 05-15-2014
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Meningioma is the second most common primary central nervous system neoplasm. In contrast, chordoid meningioma is rare; due to the paucity of cases, little is known about its clinical features or treatment outcomes. The objectives of this study were to describe the clinical characteristics and outcomes for patients with chordoid meningioma.
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Pattern of frequent but nontargeted pharmacologic thromboprophylaxis for hospitalized patients with cancer at academic medical centers: a prospective, cross-sectional, multicenter study.
J. Clin. Oncol.
PUBLISHED: 05-05-2014
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Hospitalized patients with cancer are considered to be at high risk for venous thromboembolism (VTE). Despite strong recommendations in numerous clinical practice guidelines, retrospective studies have shown that pharmacologic thromboprophylaxis is underutilized in hospitalized patients with cancer.
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Long-term effects of knitted silk-collagen sponge scaffold on anterior cruciate ligament reconstruction and osteoarthritis prevention.
Biomaterials
PUBLISHED: 05-02-2014
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Anterior cruciate ligament (ACL) is difficult to heal after injury due to the dynamic fluid environment of joint. Previously, we have achieved satisfactory regeneration of subcutaneous tendon/ligament with knitted silk-collagen sponge scaffold due to its specific "internal-space-preservation" property. This study aims to investigate the long-term effects of knitted silk-collagen sponge scaffold on ACL regeneration and osteoarthritis prevention. The knitted silk-collagen sponge scaffold was fabricated and implanted into a rabbit ACL injury model. The knitted silk-collagen sponge scaffold was found to enhance migration and adhesion of spindle-shaped cells into the scaffold at 2 months post-surgery. After 6 months, ACL treated with the knitted silk-collagen sponge scaffold exhibited increased expression of ligament genes and better microstructural morphology. After 18 months, the knitted silk-collagen sponge scaffold-treated group had more mature ligament structure and direct ligament-to-bone healing. Implanted knitted silk-collagen sponge scaffolds degraded much more slowly compared to subcutaneous implantation. Furthermore, the knitted silk-collagen sponge scaffold effectively protected joint surface cartilage and preserved joint space for up to 18 months post-surgery. These findings thus demonstrated that the knitted silk-collagen sponge scaffold can regenerate functional ACL and prevent osteoarthritis in the long-term, suggesting its clinical use as a functional bioscaffold for ACL reconstruction.
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Tpl2 induces castration resistant prostate cancer progression and metastasis.
Int. J. Cancer
PUBLISHED: 04-22-2014
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Progression to metastatic castration resistant prostate cancer (CRPC) is the major lethal pathway of prostate cancer (PC). Herein, we demonstrated that tumor progression locus 2 (Tpl2) kinase is the fundamental molecule provoking progression and metastasis of CRPC. Tpl2 upregulates CXCR4 and focal adhesion kinase (FAK) to activate CXCL12/CXCR4 and FAK/Akt signalling pathway. Consequently, epithelial-mesenchymal transition (EMT) and stemness of androgen depletion independent (ADI) PC cells are induced, which is dependent on the kinase activity of Tpl2. In vitro, proliferation, clonogenicity, migration, invasion and chemoresistance of ADI PC cells were enhanced by Tpl2. In vivo, Tpl2 overexpression and downregulation showed significant stimulatory and inhibitory effects on tumorigenic and metastatic potential of ADI PC cells, respectively. Moreover, the prognostic effects of Tpl2 and expressional correlation between Tpl2 and EMT-related molecules/CXCR4 were validated in clinical PC databases. Since Tpl2 exerts metastatic progression promoting activities in CRPC, Tpl2 could serve as a novel therapeutic target for metastatic CRPC.
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Genome-wide identification and predictive modeling of polyadenylation sites in eukaryotes.
Brief. Bioinformatics
PUBLISHED: 04-04-2014
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Polyadenylation [poly(A)] is a vital step in post-transcriptional processing of pre-mRNA. Alternative polyadenylation is a widespread mechanism of regulating gene expression in eukaryotes. Defining poly(A) sites contributes to the annotation of transcripts' ends and the study of gene regulatory mechanisms. Here, we survey methods for collecting poly(A) sites using high-throughput sequencing technologies and summarize the general processes for genome-wide poly(A) site identifications. We also compare the performances of various poly(A) site prediction models and discuss the relationship between poly(A) site identification from sequencing projects and predictive modeling. Moreover, we attempt to address some potential problems in current researches and propose future directions related to polyadenylation research.
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Transfusion-associated Anaplasma phagocytophilum infection in a pregnant patient with thalassemia trait: a case report.
Transfusion
PUBLISHED: 04-03-2014
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Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile illness caused by the bacterium Anaplasma phagocytophilum. Although usually transmitted via tick bite, HGA may rarely also be acquired through transfusion. HGA during pregnancy may pose significant gestational risks due to altered maternal immune status and the potential for perinatal transmission.
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Cyberbullying, problematic internet use, and psychopathologic symptoms among Korean youth.
Yonsei Med. J.
PUBLISHED: 04-01-2014
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To evaluate the associations between cyberbullying behaviors and problematic internet use, and to compare psychopathologic symptoms in victims, perpetrators, and victims-perpetrators of cyberbullying to those in youths who were not involved in cyberbullying. A total of 4531 youths (11-14 years of age) were recruited from elementary and middle schools. Among 4531 youths, 9.7% were involved in cyberbullying; 3.3% were only victims; 3.4% were only perpetrators; and 3.0% were victims-perpetrators. Cyberbullying behaviors were associated with problematic internet use as well as various psychopathologic symptoms. Depressive symptoms were associated with cyberbullying victimization, and rule-breaking behaviors and aggressive behaviors have relevance to cyberbullying perpetration. Greater attention needs to be paid to identify youths earlier who are involved in cyberbullying and prevent serious adverse consequences in them.
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Bioinformatics analysis of alternative polyadenylation in green alga Chlamydomonas reinhardtii using transcriptome sequences from three different sequencing platforms.
G3 (Bethesda)
PUBLISHED: 03-15-2014
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Messenger RNA 3'-end formation is an essential posttranscriptional processing step for most eukaryotic genes. Different from plants and animals where AAUAAA and its variants routinely are found as the main poly(A) signal, Chlamydomonas reinhardtii uses UGUAA as the major poly(A) signal. The advance of sequencing technology provides an enormous amount of sequencing data for us to explore the variations of poly(A) signals, alternative polyadenylation (APA), and its relationship with splicing in this algal species. Through genome-wide analysis of poly(A) sites in C. reinhardtii, we identified a large number of poly(A) sites: 21,041 from Sanger expressed sequence tags, 88,184 from 454, and 195,266 from Illumina sequence reads. In comparison with previous collections, more new poly(A) sites are found in coding sequences and intron and intergenic regions by deep-sequencing. Interestingly, G-rich signals are particularly abundant in intron and intergenic regions. The prevalence of different poly(A) signals between coding sequences and a 3'-untranslated region implies potentially different polyadenylation mechanisms. Our data suggest that the APA occurs in about 68% of C. reinhardtii genes. Using Gene Ontolgy analysis, we found most of the APA genes are involved in RNA regulation and metabolic process, protein synthesis, hydrolase, and ligase activities. Moreover, intronic poly(A) sites are more abundant in constitutively spliced introns than retained introns, suggesting an interplay between polyadenylation and splicing. Our results support that APA, as in higher eukaryotes, may play significant roles in increasing transcriptome diversity and gene expression regulation in this algal species. Our datasets also provide useful information for accurate annotation of transcript ends in C. reinhardtii.
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Hf-Nd isotopic variability in mineral dust from Chinese and Mongolian deserts: implications for sources and dispersal.
Sci Rep
PUBLISHED: 03-04-2014
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Mineral dust provenances are closely related to the orogenic processes which may have distinct Hf-Nd isotopic signatures. Here we report the clay-sized (<2 ?m) Hf-Nd isotope data from Asian dust sources to better constrain the source and transport dynamics of dust deposition in the North Pacific. Our results show that there is a more positive radiogenic Hf isotopic composition with clay-sized fractions than the corresponding bulk sample and a decoupling of the Hf-Nd couplets in the clay formation during the weathering process. The clay-sized Hf-Nd isotopic compositions of the desert samples from the Sino-Korean-Tarim Craton (SKTC) are different from those of the Gobi and deserts from the Central Asian Orogeny Belt (CAOB) due to varying tectonic and weathering controls. The Hf-Nd isotopic compositions of dust in the North Pacific central province (NPC) match closely with those from the Taklimakan, Badain Jaran and adjacent Tengger deserts, implying that the NPC dust was mainly transported from these potential sources by the westerly jet. Our study indicates that dusts from the CAOB Gobi deserts either didn't arrive in NPC or were quantitatively insignificant, but they were likely transported to the North Pacific margin province (NPM) by East Asian winter monsoon.
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Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-?B independent of NRF2-mediated mechanism.
J. Nutr. Biochem.
PUBLISHED: 02-26-2014
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The objectives of this study were to compare the anti-inflammatory effects of anthocyanins from blueberry (BBA), blackberry (BKA), and blackcurrant (BCA) and to determine the relationship between their antioxidant capacity and anti-inflammatory effect in macrophages. Major anthocyanins in BBA, BKA and BCA were malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3-rutinoside (44%), respectively. BKA showed higher total antioxidant capacity than BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 ?g/ml of BBA, BKA and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1? (IL-1?) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 ?g/ml or higher. Tumor necrosis factor ? (TNF?) mRNA levels and secretion were also significantly decreased in LPS-treated macrophages. The levels of the repression were comparable for all berry anthocyanins. LPS-induced nuclear factor ?B (NF-?B) p65 translocation to the nucleus was markedly attenuated by all of the berry anthocyanins. In bone marrow-derived macrophages (BMMs) from nuclear factor E2-related factor 2 wild-type (Nrf2(+/+)) mice, BBA, BKA and BCA significantly decreased cellular reactive oxygen species (ROS) levels with a concomitant decrease in IL-1? mRNA levels upon LPS stimulation. However, in the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly decrease IL-1? mRNA despite the fact that ROS levels were not significantly affected. In conclusion, BBA, BKA and BCA exert their anti-inflammatory effects in macrophages, at least in part, by inhibiting nuclear translocation of NF-?B independent of the NRF2-mediated pathways.
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Optimal local searching for fast and robust textureless 3D object tracking in highly cluttered backgrounds.
IEEE Trans Vis Comput Graph
PUBLISHED: 02-22-2014
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Edge-based tracking is a fast and plausible approach for textureless 3D object tracking, but its robustness is still very challenging in highly cluttered backgrounds due to numerous local minima. To overcome this problem, we propose a novel method for fast and robust textureless 3D object tracking in highly cluttered backgrounds. The proposed method is based on optimal local searching of 3D-2D correspondences between a known 3D object model and 2D scene edges in an image with heavy background clutter. In our searching scheme, searching regions are partitioned into three levels (interior, contour, and exterior) with respect to the previous object region, and confident searching directions are determined by evaluating candidates of correspondences on their region levels; thus, the correspondences are searched among likely candidates in only the confident directions instead of searching through all candidates. To ensure the confident searching direction, we also adopt the region appearance, which is efficiently modeled on a newly defined local space (called a searching bundle). Experimental results and performance evaluations demonstrate that our method fully supports fast and robust textureless 3D object tracking even in highly cluttered backgrounds.
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Do ?-conjugative effects facilitate SN2 reactions?
J. Am. Chem. Soc.
PUBLISHED: 02-13-2014
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Rigorous quantum chemical investigations of the SN2 identity exchange reactions of methyl, ethyl, propyl, allyl, benzyl, propargyl, and acetonitrile halides (X = F(-), Cl(-)) refute the traditional view that the acceleration of SN2 reactions for substrates with a multiple bond at C? (carbon adjacent to the reacting C? center) is primarily due to ?-conjugation in the SN2 transition state (TS). Instead, substrate-nucleophile electrostatic interactions dictate SN2 reaction rate trends. Regardless of the presence or absence of a C? multiple bond in the SN2 reactant in a series of analogues, attractive C?(?(+))···X(?(-)) interactions in the SN2 TS lower net activation barriers (E(b)) and enhance reaction rates, whereas repulsive C?(?(-))···X(?(-)) interactions increase E(b) barriers and retard SN2 rates. Block-localized wave function (BLW) computations confirm that ?-conjugation lowers the net activation barriers of SN2 allyl (1t, coplanar), benzyl, propargyl, and acetonitrile halide identity exchange reactions, but does so to nearly the same extent. Therefore, such orbital interactions cannot account for the large range of E(b) values in these systems.
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Outcome of conventional treatment and prognostic factor in elderly glioblastoma patients.
Acta Neurochir (Wien)
PUBLISHED: 01-30-2014
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Glioblastoma (GBM) is the most life-threatening primary brain tumour. Especially in elderly patients, a poorer outcome is noticeable. Until now, the effectiveness of the conventional active treatment has been controversial. The purpose of this study is to find the optimal treatment for elderly patients with newly diagnosed GBM.
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Efficacy of postoperative radiotherapy for high grade meningiomas.
J. Neurooncol.
PUBLISHED: 01-29-2014
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The necessity of postoperative radiotherapy (PORT) for meningiomas remains contentious. Here, the role of PORT in patients who underwent surgical resection for WHO grade II and III meningiomas was assessed. The record of 114 patients with WHO grade II (n = 72) and III (n = 42) meningiomas treated at Samsung Medical Center between March 1995 and April 2013 were reviewed and classified according to the extent of surgical resection and implementation of PORT. Median follow-up was 55.9 months. Simpson grade (SG) I, II, III, and IV resections were achieved in 29, 56, 9 and 20 patients, respectively. The 5-year local control (LC) and overall survival rate was 65.8 and 84.2 %, respectively. Thirty patients (26.3 %) developed local failure and five patients (4.4 %) developed distant metastases. The extent of surgical resection (SG I-II vs. III-IV) was influenced by tumor location (orbital and skull base lesions vs. others, p = 0.001) and the surgeons' experience (>10 operations, p = 0.044). Extent of surgical resection was also associated with local failure, overall progression, and overall survival (p = 0.001, p < 0.001, and p < 0.001, respectively). PORT improved LC in patients with incomplete surgical resection (SG III-IV, p = 0.049). Complete resection (SG I-II) is an important prognostic factor for LC and survival, and the extent of surgical resection (SG I-II vs. III-IV) is influenced by tumor location. PORT could improve the LC in WHO grade II-III meningioma patients who underwent incomplete surgical resection (SG III-IV).
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On the large ?-hyperconjugation in alkanes and alkenes.
J Mol Model
PUBLISHED: 01-22-2014
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The conventional view that the ?CC and ?CH bonds in alkanes and unsaturated hydrocarbons are so highly localized that their non-steric interactions are negligible is scrutinized by the block-localized wavefunction (BLW) method. Even molecules considered conventionally to be "strain free" and "unperturbed" have surprisingly large and quite significant total ?-BLW-delocalization energies (DEs) due to their geminal and vicinal hyperconjugative interactions. Thus, the computed BLW-DEs (in kcal mol(-1)) for the antiperiplanar conformations of the n-alkanes (C(N)H(2N+2), N = 1-10) range from 11.6 for ethane to 82.2 for?n-decane and are 50.9 for cyclohexane and 91.0 for adamantane. Although ?-electron delocalization in unsaturated hydrocarbons usually is ignored, the ?-BLW-DEs (in kcal mol(-1)) are substantial, as exemplified by D2h ethylene (9.0), triplet D2d ethylene (16.4), allene (19.3), butadiene (19.0), hexatriene (28.3), benzene (28.1), and cyclobutadiene (21.1). While each individual geminal and vicinal hyperconjugative interaction between hydrocarbon ?-bonding and ?-antibonding orbitals tends to be smaller than an individual ? conjugative interaction (e.g., 10.2 kcal mol(-1) in anti-1,3-butadiene, the presence of many ?-hyperconjugative interactions (e.g., a total of 12 in anti-1,3-butadiene, see text), result in substantial total ?-stabilization energies (e.g., 19.0 kcal mol(-1) for butadiene), which may surpass those from the ? interactions. Although large in magnitude, ?-electron delocalization energies often are obscured by cancellation when two hydrocarbons are compared. Rather than being strain-free, cyclohexane, adamantane, and diamantane suffer from their increasing number of intramolecular 1,4-C…C repulsions resulting in elongated C-C bond lengths and reduced ?-hyperconjugation, compared to the (skew-free) antiperiplanar n-alkane conformers. Instead of being inconsequential, ?-bond interactions are important and merit consideration.
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Intra-articular injection of human meniscus stem/progenitor cells promotes meniscus regeneration and ameliorates osteoarthritis through stromal cell-derived factor-1/CXCR4-mediated homing.
Stem Cells Transl Med
PUBLISHED: 01-21-2014
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Meniscus injury is frequently encountered in clinical practice. Current surgical therapy involving partial or complete meniscectomy relieves pain in the short-term but often leads to osteoarthritis (OA) in the long-term. In this study, we report a new strategy of articular cartilage protection by intra-articular injection of novel human meniscus stem/progenitor cells (hMeSPCs). We found that hMeSPCs displayed both mesenchymal stem cell characteristics and high expression levels of collagen II. In the rat meniscus injury model, hMeSPC transplantation not only led to more neo-tissue formation and better-defined shape but also resulted in more rounded cells and matured extracellular matrix. Stromal cell-derived factor-1 (SDF-1) enhanced the migration of hMeSPCs, whereas AMD3100 abolished the chemotactic effects of SDF-1 on hMeSPCs, both in vitro and in vivo. In an experimental OA model, transplantation of hMeSPCs effectively protected articular cartilage, as evidenced by reduced expression of OA markers such as collagen I, collagen X, and hypoxia-inducible factor 2? but increased expression of collagen II. Our study demonstrated for the first time that intra-articular injection of hMeSPCs enhanced meniscus regeneration through the SDF-1/CXCR4 axis. Our study highlights a new strategy of intra-articular injection of hMeSPCs for meniscus regeneration.
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Programming a Pavlovian-like conditioning circuit in Escherichia coli.
Nat Commun
PUBLISHED: 01-18-2014
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Synthetic genetic circuits are programmed in living cells to perform predetermined cellular functions. However, designing higher-order genetic circuits for sophisticated cellular activities remains a substantial challenge. Here we program a genetic circuit that executes Pavlovian-like conditioning, an archetypical sequential-logic function, in Escherichia coli. The circuit design is first specified by the subfunctions that are necessary for the single simultaneous conditioning, and is further genetically implemented using four function modules. During this process, quantitative analysis is applied to the optimization of the modules and fine-tuning of the interconnections. Analogous to classical Pavlovian conditioning, the resultant circuit enables the cells to respond to a certain stimulus only after a conditioning process. We show that, although the conditioning is digital in single cells, a dynamically progressive conditioning process emerges at the population level. This circuit, together with its rational design strategy, is a key step towards the implementation of more sophisticated cellular computing.
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Planar Möbius aromatic pentalenes incorporating 16 and 18 valence electron osmiums.
Nat Commun
PUBLISHED: 01-15-2014
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Aromaticity, a highly stabilizing feature of molecules with delocalized electrons in closed circuits, is generally restricted to 'Hückel' systems with 4n+2 mobile electrons. Although the Möbius concept extends the principle of aromaticity to 4n mobile electron species, the rare known examples have complex, twisted topologies whose extension is unlikely. Here we report the realization of osmapentalenes, the first planar Möbius aromatic complexes with 16 and 18 valence electron transition metals. The Möbius aromaticity of these osmapentalenes, documented by X-ray structural, magnetic and theoretical analyses, demonstrates the basis of the aromaticity of the parent osmapentalynes. All these osmapentalenes are formed by both electrophilic and nucleophilic reactions of the in-plane ? component of the same carbyne carbon, illustrating ambiphilic carbyne reactivity, which is seldom observed in transition metal chemistry. Our results widen the scope of Möbius aromaticity dramatically and open prospects for the generalization of planar Möbius aromatic chemistry.
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PMA synergistically enhances apicularen A-induced cytotoxicity by disrupting microtubule networks in HeLa cells.
BMC Cancer
PUBLISHED: 01-15-2014
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Combination therapy is key to improving cancer treatment efficacy. Phorbol 12-myristate 13-acetate (PMA), a well-known PKC activator, increases the cytotoxicity of several anticancer drugs. Apicularen A induces cytotoxicity in tumor cells through disrupting microtubule networks by tubulin down-regulation. In this study, we examined whether PMA increases apicularen A-induced cytotoxicity in HeLa cells.
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Antioxidant supplementation reduces genomic aberrations in human induced pluripotent stem cells.
Stem Cell Reports
PUBLISHED: 01-14-2014
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Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using oncogenic transcription factors. However, this method leads to genetic aberrations in iPSCs via unknown mechanisms, which may limit their clinical use. Here, we demonstrate that the supplementation of growth media with antioxidants reduces the genome instability of cells transduced with the reprogramming factors. Antioxidant supplementation did not affect transgene expression level or silencing kinetics. Importantly, iPSCs made with antioxidants had significantly fewer de novo copy number variations, but not fewer coding point mutations, than iPSCs made without antioxidants. Our results suggest that the quality and safety of human iPSCs might be enhanced by using antioxidants in the growth media during the generation and maintenance of iPSCs.
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Mutations and expression of PmrAB and PhoPQ related with colistin resistance in Pseudomonas aeruginosa clinical isolates.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 01-14-2014
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To comprehend the resistance of colistin resistance, we investigated the relationships between amino acid alterations and expression of PmrAB and PhoPQ and colistin resistance in 16 colistin-nonsusceptible clinical Pseudomonas aeruginosa isolates. In addition, we obtained induced colistin-resistant mutants and their colistin-susceptible revertants. Expression levels of the pmrA, phoP, parR, cprR, and pmrH genes were determined for them. Nine amino acid substitutions unique to 10 colistin-nonsusceptible P. aeruginosa (CNPA) isolates were identified: 7 in PmrB and 1 each in PmrA and PhoQ. However, 6 CNPA isolates did not show amino acid substitutions compared with colistin-susceptible P. aeruginosa isolates. Among 16 CNPA isolates, 7 and 8 isolates displayed activated expression of pmrA and phoP, respectively. Activated expression of pmrA and/or phoP was identified in 13 isolates of CNPA isolates, but some had no noticeable PmrAB and PhoPQ amino acid substitutions. In addition, in vitro selected colistin-resistant mutants (P5R and P155R) showed higher expression level in pmrA, phoP, and pmrH than their parent strains (P5 and P155) and colistin-susceptible, revertant strains (P5R-rev and P155R-rev). However, expression of the parR and cprR genes was not consistent. Our data may indicate that amino acid substitutions of PmrAB or PhoPQ do not have an immediate connection with decreased susceptibility of colistin in P. aeruginosa isolates, although activated expression of pmrAB and/or phoPQ resulting in overexpression of pmrH may be required for colistin resistance. Expression of pmrAB or phoPQ related with colistin nonsusceptibility may not explained by a single mechanism, which may suggest that colistin resistance appears easily by diverse pathways in clinical settings as well as in laboratory.
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Predictors of suicidal ideation in a community sample: roles of anger, self-esteem, and depression.
Psychiatry Res
PUBLISHED: 01-09-2014
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The objective of this cross-sectional study was to investigate the relationships of anger, self-esteem, and depression with suicidal ideation. A survey was conducted in a wide range of community areas across Jeollabuk-do Province, Korea. A total of 2964 subjects (mean age=44.4yr) participated in this study. Hierarchical regression was used to investigate predictors of suicidal ideation in terms of their sociodemographic characteristics, depression, self-esteem, and anger. Hierarchical regression analyses revealed that anger and self-esteem were significantly associated with suicidal ideation regardless of age and after controlling for depression. Moderation analysis showed that the impact of anger on suicidal ideation was significantly greater among females than males in adolescents, but not in other age groups. Additionally, there were some differences in sociodemographic predictors of suicidal ideation among age groups. Predictors included gender and family harmony in adolescents, marital status and family harmony in middle-aged individuals, and economic status and family harmony in elderly individuals. Our results revealed that anger and self-esteem play important roles in suicidal ideation beyond the effect of depression. Development and implementation of preventive strategies, including management of anger and self-esteem, could possibly reduce suicidal ideation and subsequent suicide attempts.
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Effect of imaging time in the magnetic resonance detection of intracerebral metastases using single dose gadobutrol.
Korean J Radiol
PUBLISHED: 01-08-2014
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To compare the effect of imaging time delay on the MR detection of intracerebral metastases using single dose gadobutrol.
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detectIR: A Novel Program for Detecting Perfect and Imperfect Inverted Repeats Using Complex Numbers and Vector Calculation.
PLoS ONE
PUBLISHED: 01-01-2014
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Inverted repeats are present in abundance in both prokaryotic and eukaryotic genomes and can form DNA secondary structures - hairpins and cruciforms that are involved in many important biological processes. Bioinformatics tools for efficient and accurate detection of inverted repeats are desirable, because existing tools are often less accurate and time consuming, sometimes incapable of dealing with genome-scale input data. Here, we present a MATLAB-based program called detectIR for the perfect and imperfect inverted repeat detection that utilizes complex numbers and vector calculation and allows genome-scale data inputs. A novel algorithm is adopted in detectIR to convert the conventional sequence string comparison in inverted repeat detection into vector calculation of complex numbers, allowing non-complementary pairs (mismatches) in the pairing stem and a non-palindromic spacer (loop or gaps) in the middle of inverted repeats. Compared with existing popular tools, our program performs with significantly higher accuracy and efficiency. Using genome sequence data from HIV-1, Arabidopsis thaliana, Homo sapiens and Zea mays for comparison, detectIR can find lots of inverted repeats missed by existing tools whose outputs often contain many invalid cases. detectIR is open source and its source code is freely available at: https://sourceforge.net/projects/detectir.
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Aberrant DNA methylation reprogramming during induced pluripotent stem cell generation is dependent on the choice of reprogramming factors.
Cell Regen (Lond)
PUBLISHED: 01-01-2014
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The conversion of somatic cells into pluripotent stem cells via overexpression of reprogramming factors involves epigenetic remodeling. DNA methylation at a significant proportion of CpG sites in induced pluripotent stem cells (iPSCs) differs from that of embryonic stem cells (ESCs). Whether different sets of reprogramming factors influence the type and extent of aberrant DNA methylation in iPSCs differently remains unknown. In order to help resolve this critical question, we generated human iPSCs from a common fibroblast cell source using either the Yamanaka factors (OCT4, SOX2, KLF4 and cMYC) or the Thomson factors (OCT4, SOX2, NANOG and LIN28), and determined their genome-wide DNA methylation profiles. In addition to shared DNA methylation aberrations present in all our iPSCs, we identified Yamanaka-iPSC (Y-iPSC)-specific and Thomson-iPSC (T-iPSC)-specific recurrent aberrations. Strikingly, not only were the genomic locations of the aberrations different but also their types: reprogramming with Yamanaka factors mainly resulted in failure to demethylate CpGs, whereas reprogramming with Thomson factors mainly resulted in failure to methylate CpGs. Differences in the level of transcripts encoding DNMT3b and TET3 between Y-iPSCs and T-iPSCs may contribute partially to the distinct types of aberrations. Finally, de novo aberrantly methylated genes in Y-iPSCs were enriched for NANOG targets that are also aberrantly methylated in some cancers. Our study thus reveals that the choice of reprogramming factors influences the amount, location, and class of DNA methylation aberrations in iPSCs. These findings may provide clues into how to produce human iPSCs with fewer DNA methylation abnormalities.
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Gene expression responses of threespine stickleback to salinity: implications for salt-sensitive hypertension.
Front Genet
PUBLISHED: 01-01-2014
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Despite recent success with genome-wide association studies (GWAS), identifying hypertension (HTN)-susceptibility loci in the general population remains difficult. Here, we present a novel strategy to address this challenge by studying salinity adaptation in the threespine stickleback, a fish species with diverse salt-handling ecotypes. We acclimated native freshwater (FW) and anadromous saltwater (SW) threespine sticklebacks to fresh, brackish, and sea water for 30 days, and applied RNA sequencing to determine the gene expression in fish kidneys. We identified 1844 salt-responsive genes that were differentially expressed between FW sticklebacks acclimated to different salinities and/or between SW and FW sticklebacks acclimated to full-strength sea water. Significant overlap between stickleback salt-responsive genes and human genes implicated in HTN was detected (P < 10(-7), hypergeometric test), suggesting a possible similarity in genetic mechanisms of salt handling between threespine sticklebacks and humans. The overlapping genes included a newly discovered HTN gene-MAP3K15, whose expression in FW stickleback kidneys decreases with salinity. These also included genes located in the GWAS loci such as AGTRAP-PLOD1 and CYP1A1-ULK3, which contain multiple potentially causative genes contributing to HTN susceptibility that need to be prioritized for study. Taken together, we show that stickleback salt-responsive genes provide valuable information facilitating the identification of human HTN genes. Thus, threespine sticklebacks may be used as a model, complementary to existing animal models, in human HTN research.
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Translational validation of personalized treatment strategy based on genetic characteristics of glioblastoma.
PLoS ONE
PUBLISHED: 01-01-2014
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Glioblastoma (GBM) heterogeneity in the genomic and phenotypic properties has potentiated personalized approach against specific therapeutic targets of each GBM patient. The Cancer Genome Atlas (TCGA) Research Network has been established the comprehensive genomic abnormalities of GBM, which sub-classified GBMs into 4 different molecular subtypes. The molecular subtypes could be utilized to develop personalized treatment strategy for each subtype. We applied a classifying method, NTP (Nearest Template Prediction) method to determine molecular subtype of each GBM patient and corresponding orthotopic xenograft animal model. The models were derived from GBM cells dissociated from patient's surgical sample. Specific drug candidates for each subtype were selected using an integrated pharmacological network database (PharmDB), which link drugs with subtype specific genes. Treatment effects of the drug candidates were determined by in vitro limiting dilution assay using patient-derived GBM cells primarily cultured from orthotopic xenograft tumors. The consistent identification of molecular subtype by the NTP method was validated using TCGA database. When subtypes were determined by the NTP method, orthotopic xenograft animal models faithfully maintained the molecular subtypes of parental tumors. Subtype specific drugs not only showed significant inhibition effects on the in vitro clonogenicity of patient-derived GBM cells but also synergistically reversed temozolomide resistance of MGMT-unmethylated patient-derived GBM cells. However, inhibitory effects on the clonogenicity were not totally subtype-specific. Personalized treatment approach based on genetic characteristics of each GBM could make better treatment outcomes of GBMs, although more sophisticated classifying techniques and subtype specific drugs need to be further elucidated.
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Green lighting upconversion luminescence of Yb3+, Er3+ co-doped BaMoO4.
J Nanosci Nanotechnol
PUBLISHED: 11-12-2013
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A green lighting upconversion (UC) system was successfully achieved from Er3+/Yb3+ co-doped BaMoO4 synthesized by the complex citrate-gel method. Under 980 nm laser excitation, the Er3+/Yb3+ co-doped BaMoO4 emitted strong green luminescence around 530 and 550 nm and weak red luminescence near 660 nm, which corresponded to the intra 4f-4f transitions in Er3+. Optimal doping concentrations of Er3+/Yb3+ into the BaMoO4 matrix were investigated. Moreover, based on excitation power dependence, the UC luminescent mechanism in the Er3+/Yb3+ co-doped BaMoO4 was presented in detail.
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Comparison of the Pharmacokinetics, Safety, and Tolerability of Vitamin D3 in DP-R206 (150-mg Ibandronate/24,000-IU Vitamin D3 Tablet) and as Monotherapy (24,000 IU) in Healthy Male Korean Adults.
Clin Ther
PUBLISHED: 09-09-2013
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Combined treatment with a bisphosphonate and vitamin D has been proposed for postmenopausal osteoporosis. A new, fixed-dose combination tablet of ibandronate plus vitamin D3 has been developed for monthly administration to treat postmenopausal osteoporosis.
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Alpha-smooth muscle actin (ACTA2) is required for metastatic potential of human lung adenocarcinoma.
Clin. Cancer Res.
PUBLISHED: 08-30-2013
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Metastatic relapse of primary lung cancer leads to therapeutic resistance and unfavorable clinical prognosis; therefore, identification of key molecules associated with metastatic conversion has significant clinical implications. We previously identified a link between early brain metastasis of lung adenocarcinoma and amplification of the ?-smooth muscle actin (ACTA2) gene. The aim of present study was to investigate the prognostic and functional significance of ACTA2 expression in cancer cells for the metastatic potential of lung adenocarcinomas.
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Tpl2 kinase impacts tumor growth and metastasis of clear cell renal cell carcinoma.
Mol. Cancer Res.
PUBLISHED: 08-27-2013
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Due to the innate high metastatic ability of renal cell carcinoma (RCC), many patients with RCC experience local or systemic relapses after surgical resection. A deeper understanding of the molecular pathogenesis underlying advanced RCC is essential for novel innovative therapeutics. Tumor progression locus 2 (Tpl2), upregulated in various tumor types, has been reported to be associated with oncogenesis and metastatic progression via activation of the MAPK signaling pathway. Herein, the relevance of Tpl2 in tumor growth and metastasis of RCC is explored. Inspection of The Cancer Genome Atlas (TCGA) indicated that Tpl2 overexpression was significantly related to the presence of metastases and poor outcome in clear cell RCC (ccRCC), which is the most aggressive subtype of RCC. Moreover, expression of Tpl2 and CXCR4 showed a positive correlation in ccRCC patients. Depletion of Tpl2 by RNAi or activity by a Tpl2 kinase inhibitor in human ccRCC cells remarkably suppressed MAPK pathways and impaired in vitro cell proliferation, clonogenicity, anoikis resistance, migration, and invasion capabilities. Similarly, orthotopic xenograft growth and lung metastasis were significantly inhibited by Tpl2 silencing. Furthermore, Tpl2 knockdown reduced CXCL12-directed chemotaxis and chemoinvasion accompanied with impaired downstream signaling, indicating potential involvement of Tpl2 in CXCR4-mediated metastasis. Taken together, these data indicate that Tpl2 kinase is associated with and contributes to disease progression of ccRCC. Implications: Tpl2 kinase activity has prognostic and therapeutic targeting potential in aggressive clear cell renal cell carcinoma.
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17?-Estradiol Protects Human Eyelid-Derived Adipose Stem Cells against Cytotoxicity and Increases Transplanted Cell Survival in Spinal Cord injury.
J. Cell. Mol. Med.
PUBLISHED: 07-09-2013
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Stem cell transplantation represents a promising strategy for the repair of spinal cord injury (SCI). However, the low survival rate of the grafted cells is a major obstacle hindering clinical success because of ongoing secondary injury processes, which includes excitotoxicity, inflammation and oxidative stress. Previous studies have shown that 17b-estradiol (E2) protects several cell types against cytotoxicity. Thus, we examined the effects of E2 on the viability of human eyelid adipose-derived stem cells (hEASCs) in vitro with hydrogen peroxide (H2 O2 )-induced cell model and in vivo within a rat SCI model. Our results showed that E2 protected hEASCs against H2 O2 -induced cell death in vitro, and enhanced the survival of grafted hEASCs in vivo by reducing apoptosis. Additionally, E2 also enhanced the secretion of growth factors by hEASCs, thereby making the local microenvironment more conducive for tissue regeneration. Overall, E2 administration enhanced the therapeutic efficacy of hEASCs transplantation and facilitated motor function recovery after SCI. Hence, E2 administration may be an intervention of choice for enhancing survival of transplanted hEASCs after SCI.
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Gamma knife radiosurgery for brain metastases from breast cancer.
J Korean Neurosurg Soc
PUBLISHED: 06-26-2013
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The authors conducted a retrospective cohort study to determine prognostic factors and treatment outcomes of brain metastases (BM) from breast cancer (BC) after Gamma Knife radiosurgery (GKS).
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Lack of evidence to support thromboprophylaxis in hospitalized medical patients with cancer.
Am. J. Med.
PUBLISHED: 06-24-2013
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The administration of anticoagulant thromboprophylaxis for all patients with cancer who are hospitalized for acute medical illness is considered standard practice and strongly recommended in clinical guidelines. These recommendations are extrapolated from randomized controlled prophylaxis trials not specifically conducted in cancer cohorts. Because hospitalized patients with cancer constitute a unique population with increased risk of venous thromboembolic events and major hemorrhage, validation of the efficacy and safety of primary thromboprophylaxis in this population is critical. We sought to summarize the rates of venous thromboembolic events and major bleeding episodes among hospitalized patients with cancer who were receiving anticoagulant therapy compared with placebo.
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Optimal Local Searching for Fast and Robust Textureless 3D Object Tracking in Highly Cluttered Backgrounds.
IEEE Trans Vis Comput Graph
PUBLISHED: 06-19-2013
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Edge-based tracking is a fast and plausible approach for textureless 3D object tracking, but its robustness is still very challenging in highly cluttered backgrounds due to numerous local minima. To overcome this problem, we propose a novel method for fast and robust textureless 3D object tracking in highly cluttered backgrounds. The proposed method is based on optimal local searching of 3D-2D correspondences between a known 3D object model and 2D scene edges in an image with heavy background clutter. In our searching scheme, searching regions are partitioned into three levels (interior, contour, and exterior) with respect to the previous object region, and confident searching directions are determined by evaluating candidates of correspondences on their region levels; thus, the correspondences are searched among likely candidates in only the confident directions instead of searching through all candidates. To ensure the confident searching direction, we also adopt the region appearance, which is efficiently modeled on a newly defined local space (called a searching bundle). Experimental results and performance evaluations demonstrate that our method fully supports fast and robust textureless 3D object tracking even in highly cluttered backgrounds.
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Smoking among individuals with schizophrenia in Korea: gender differences.
Arch Psychiatr Nurs
PUBLISHED: 06-11-2013
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This study examined gender differences in smoking and quitting among individuals diagnosed with schizophrenia in Korea. In addition, the study investigated differences in caffeine use by gender and smoking status.
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Development and validation of an LC-MS/MS method for determination of compound K in human plasma and clinical application.
J Ginseng Res
PUBLISHED: 05-30-2013
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A rapid, sensitive and selective analytical method was developed and validated for the determination of compound K, a major intestinal bacterial metabolite of ginsenosides in human plasma. Liquid-liquid extraction was used for sample preparation and analysis, followed by liquid chromatography tandem spectrometric analysis and an electrospray-ionization interface. Compound K was analyzed on a Phenomenex Luna C18 column (100×2.00 mm, 3 ?m) with the mobile phase run isocratically with 10 mM ammonium acetate-methanol-acetonitrile (5:47.5:47.5, v/v/v) at a flow rate of 0.5 mL/min. The method was validated for accuracy (relative error <12.63%), precision (coefficient of variation <9.14%), linearity, and recovery. The assay was linear over the entire range of calibration standards i.e., a concentration range of 1 ng/mL to 1,000 ng/ mL (r (2) >0.9968). The recoveries of compound K after liquid-liquid extraction at 1, 2, 400, and 800 ng/mL were 106.00±0.08%, 103.50±0.19%, 111.45±5.21%, and 89.62±34.46% for intra-day and 85.40±0.08%, 94.50±0.09%, 112.50±5.21%, and 95.87±34.46% for inter-day, respectively. The lower limit of quantification of the analytical method of compound K was 1 ng/ mL in human plasma. The developed method was successfully applied to a pharmacokinetic study of compound K after oral administration in ten of healthy human subjects.
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Frontal sinus surgery anterior to the ethmoid bulla.
Int Surg
PUBLISHED: 05-25-2013
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Abstract The frontal sinus surgery is difficult to perform but the ethmoid bulla is a relative, constant landmark in the middle turbinate that can improve the surgery. The purpose of this study was to evaluate the validity, security, and predominance of approaches to the frontal sinus via the route anterior to the ethmoid bulla. The data from 370 endoscopic frontal sinus surgery cases from our center were integrated and retrospectively analyzed. Three hundred twenty-nine patients underwent frontal sinus surgery via the route anterior to the ethmoid bulla. An additional 27 patients underwent frontal sinus surgery with mini-trephination, 13 patients with the Draf II procedure, and 1 patient had applied MELP (modified endoscopic Lothrop procedure). No serious complications occurred; however, there were 3 cases of eyelid ecchymosis and 1 case of anterior ethmoid artery bleeding. In all, 319 patients (86.2%) were cured, an improvement was noted in 36 of the patients (9.7%), and there was no improvement in 15 patients (4.1%). Frontal sinus surgery via the route anterior to the ethmoid bulla is valid, relatively safe, and can be applied in most cases involving frontal disease.
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Characteristics of lead geochemistry and the mobility of Pb isotopes in the system of pedogenic rock-pedosphere-irrigated riverwater-cereal-atmosphere from the Yangtze River delta region, China.
Chemosphere
PUBLISHED: 05-22-2013
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Knowledge of the characteristics of Pb and its isotopic transfer in different compartments is scant, especially for the mobility of Pb isotopes in the geochemical cycle. The present study characterizes differential Pb transport mechanism and the mobility of Pb isotopes in the pedogenic parent rock-pedosphere-irrigated riverwater-cereal-atmosphere system in the Yangtze River delta region, by determining Pb concentration and Pb isotopic ratios of pedogenic parent rocks, fluvial suspended particle matter, tillage soils, soil profiles, irrigated riverwater, fertilizer, Pb ore, cereal roots and grains. The results show that Pb isotopes in the geochemical cycle generally follow the equation of (208)Pb/(206)Pb=-1.157×(206)Pb/(207)Pb+3.46 (r(2)=0.941). However, Pb isotopes have different mobility in different environmental matrixes. Whereas in the pedosphere, the heavier Pb ((208)Pb) usually shows stronger mobility relative to the lighter Pb, and is more likely to transfer into soil exchangeable Pb fraction and carbonates phase. The lighter Pb shows stronger transfer ability from soil to cereal grain via root compared to the heavier Pb. However, the cereal grains have lower (206)Pb/(207)Pb and higher (208)Pb/(206)Pb ratios than root and tillage soil, similar to the airborne Pb and anthropogenic Pb, implying that a considerable amount of Pb in cereal grains comes from the atmosphere. The estimate model shows that 16.7-52.6% (average: 33.5%) of Pb in rice grain is the airborne Pb.
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Gene silencing of c-Met leads to brain metastasis inhibitory effects.
Clin. Exp. Metastasis
PUBLISHED: 04-09-2013
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An unfortunate consequence of improvements in the treatments of advanced primary cancers is the concurrent increase of metastatic brain tumors. Despite of unfavorable clinical prognosis, radiation therapy is still the only viable treatment option for brain metastases. Expression of c-Met induces cell migration and invasion in many cancers, which are indispensable steps for metastasis. Accordingly, we examined the effects of gene silencing of c-Met on brain metastasis to evaluate the possibility of c-Met as a potential target. MDA-MB-435 cells were transfected with c-Met targeting short hairpin RNAs (shRNAs). Effects of c-Met shRNAs on the expression of epithelial mesenchymal transition (EMT) related proteins, in vitro migration, and in vivo brain metastasis were examined. Expression of mesenchymal markers and in vitro migration of MDA-MB-435 cells were significantly inhibited by introduction of c-Met shRNAs. When c-Met-silenced MDA-MB-435 cells were stereotactically implanted into the brains of immune-compromised mice or injected into the right internal carotid arteries, c-Met-silenced MDA-MB-435 cells produced significantly smaller tumor masses or survival time was significantly prolonged, respectively, compared with MDA-MB-435 cells transfected with control shRNA. The data reveal the novel function of c-Met in the process of brain metastasis and its potential as a preventive and/or therapeutic target in this disease.
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Osteoarthritis prevention through meniscal regeneration induced by intra-articular injection of meniscus stem cells.
Stem Cells Dev.
PUBLISHED: 04-01-2013
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Meniscus injury is frequently encountered in clinical practice. Current surgical therapy involving partial or complete meniscectomy relieves pain in the short-term but often leads to osteoarthritis (OA) in the long-term. Here, this study aimed to identify and characterize a novel population of meniscus-derived stem cells (MeSCs) and develop a new strategy of articular cartilage protection by intra-articular injection of these cells. The "stemness" and immune properties of MeSCs were investigated in vitro, while the efficacy of intra-articular injection of MeSCs for meniscus regeneration and OA prevention were investigated in vivo at 4, 8, and 12 weeks postsurgery. MeSCs displayed typical stem cell characteristics such as low immunogenicity and even possessed immunosuppressive function. In a rabbit meniscus injury model, transplantation of allogenous MeSCs did not elicit immunological rejection, but promoted neo-tissue formation with better-defined shape and more matured extracellular matrix. In a rabbit experimental OA model, transplantation of MeSCs further protected joint surface cartilage and maintained joint space at 12 weeks postsurgery, whereas extensive joint surface irregularities and joint space stenosis were observed in the control group. This study thus evoked a new strategy for articular cartilage protection and meniscus regeneration by intra-articular injection of MeSCs for patients undergoing meniscectomy.
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Apicularen A acetate induces cell death via AIF translocation and disrupts the microtubule network by down-regulating tubulin in HM7 human colon cancer cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-20-2013
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Apicularen A is a novel antitumor agent and strongly induces death in tumor cells. In this study, we synthesized apicularen A acetate, an acetyl derivative of apicularen A, and investigated its antitumor effect and mechanism in HM7 colon cancer cells. Apicularen A acetate induced apoptotic cell death and caspase-3 activation; however, the pan-caspase inhibitor Z-VAD-fmk could not prevent this cell death. Apicularen A acetate induced the loss of mitochondrial membrane potential and the translocation of apoptosis-inducing factor (AIF) from mitochondria. In addition, apicularen A acetate significantly decreased tubulin mRNA and protein levels and induced disruption of microtubule networks. Taken together, these results indicate that the mechanism of apicularen A acetate involves caspase-independent apoptotic cell death and disruption of microtubule architecture.
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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.