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Find video protocols related to scientific articles indexed in Pubmed.
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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Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.
Gut
PUBLISHED: 11-20-2014
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Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population.
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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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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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Identification of a novel ARL13B variant in a Joubert syndrome-affected patient with retinal impairment and obesity.
Eur. J. Hum. Genet.
PUBLISHED: 08-20-2014
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Joubert syndrome (JS) is a genetically heterogeneous autosomal recessive ciliopathy with 22 genes implicated to date, including a small, ciliary GTPase, ARL13B. ARL13B is required for cilia formation in vertebrates. JS patients display multiple symptoms characterized by ataxia due to the cerebellar vermis hypoplasia, and that can also include ocular abnormalities, renal cysts, liver fibrosis or polydactyly. These symptoms are shared with other ciliopathies, some of which display additional phenotypes, such as obesity. Here we identified a novel homozygous missense variant in ARL13B/JBTS8 in a JS patient who displayed retinal defects and obesity. We demonstrate the variant disrupts ARL13B function, as its expression did not rescue the mutant phenotype either in Arl13b(scorpion) zebrafish or in Arl13b(hennin) mouse embryonic fibroblasts, while the wild-type ARL13B did. Finally, we show that ARL13B is localized within the primary cilia of neonatal mouse hypothalamic neurons consistent with the known link between hypothalamic ciliary function and obesity. Thus our data identify a novel ARL13B variant that causes JS and retinopathy and suggest an extension of the phenotypic spectrum of ARL13B mutations to obesity.European Journal of Human Genetics advance online publication, 20 August 2014; doi:10.1038/ejhg.2014.156.
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Apolipoprotein e likely contributes to a maturation step of infectious hepatitis C virus particles and interacts with viral envelope glycoproteins.
J. Virol.
PUBLISHED: 08-13-2014
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The assembly of infectious hepatitis C virus (HCV) particles is tightly linked to components of the very-low-density lipoprotein (VLDL) pathway. We and others have shown that apolipoprotein E (ApoE) plays a major role in production of infectious HCV particles. However, the mechanism by which ApoE contributes to virion assembly/release and how it gets associated with the HCV particle is poorly understood. We found that knockdown of ApoE reduces titers of infectious intra- and extracellular HCV but not of the related dengue virus. ApoE depletion also reduced amounts of extracellular HCV core protein without affecting intracellular core amounts. Moreover, we found that ApoE depletion affected neither formation of nucleocapsids nor their envelopment, suggesting that ApoE acts at a late step of assembly, such as particle maturation and infectivity. Importantly, we demonstrate that ApoE interacts with the HCV envelope glycoproteins, most notably E2. This interaction did not require any other viral proteins and depended on the transmembrane domain of E2 that also was required for recruitment of HCV envelope glycoproteins to detergent-resistant membrane fractions. These results suggest that ApoE plays an important role in HCV particle maturation, presumably by direct interaction with viral envelope glycoproteins.
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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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A prospective, randomized, double-blind, and multicenter trial of prophylactic effects of ramosetronon postoperative nausea and vomiting (PONV) after craniotomy: comparison with ondansetron.
BMC Anesthesiol
PUBLISHED: 08-04-2014
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Craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). This prospective, randomized, double-blind, multi-center study was performed to evaluate the efficacy of prophylactic ramosetron in preventing PONV compared with ondansetron after elective craniotomy in adult patients.
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A dip-stick type biosensor using bioluminescent bacteria encapsulated in color-coded alginate microbeads for detection of water toxicity.
Analyst
PUBLISHED: 07-25-2014
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The use of genetically engineered bioluminescent bacteria, in which bioluminescence is induced by different modes of toxic action, represents an alternative to acute toxicity tests using living aquatic organisms (plants, vertebrates, or invertebrates) in an aqueous environment. A number of these bacterial strains have been developed, but there have been no attempts to develop a hand-held type of biosensor for monitoring or identification of toxicity. We report a facile dip-stick type biosensor using genetically engineered bioluminescent bacteria as a new platform for classification and identification of toxicity in water environments. This dip-stick type biosensor is composed of eight different optically color-coded functional alginate beads that each encapsulates a different bioluminescent bacterial strain and its corresponding fluorescent microbead. These color-coded microbeads exhibit easy identification of encapsulated microbeads, since each microbead has a different color code depending on the bioluminescent bacterial strain contained and improved cell-stability compared to liquid culture. This dip-stick type biosensor can discriminate different modes of toxic actions (i.e. DNA damage, oxidative damage, cell-membrane damage, or protein damage) of sample water tested by simply dipping the stick into the water samples. It was found that each color-coded microbead emitted distinct bioluminescence, and each dip-stick type biosensor showed different bioluminescence patterns within 2 hours, depending on the toxic chemicals contained in LB medium, tap water, or river water samples. This dip-stick type biosensor can, therefore, be widely and practically used in checking toxicity of water in the environment primarily in situ, possibly indicating the status of biodiversity.
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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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Development of colistin resistance in pmrA-, phoP-, parR- and cprR-inactivated mutants of Pseudomonas aeruginosa.
J. Antimicrob. Chemother.
PUBLISHED: 07-02-2014
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Colistin susceptibility in Pseudomonas aeruginosa is associated with a lipopolysaccharide (LPS) structure that is controlled by the modulation of several two-component regulatory systems. In this study, we attempted to elucidate the role of these two-component systems in the development of colistin resistance in P. aeruginosa.
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Effects of Asiasari radix on the morphology and viability of mesenchymal stem cells derived from the gingiva.
Mol Med Rep
PUBLISHED: 06-17-2014
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Medicinal herbs used in traditional Oriental medicine, which have been in use clinically for thousands of years, are attractive sources of novel therapeutics or preventatives. Asiasari radix (A. radix) has been suggested for use in the treatment of dental diseases, including toothache and aphthous stomatitis. The aim of this study was to evaluate the effects of A. radix extracts on the morphology and viability of human stem cells derived from the gingiva. An Asiasarum heterotropoides extract was centrifuged and freeze-dried in a lyophilizer. Stem cells derived from the gingiva were grown in the presence of A. radix at concentrations ranging between 0.1 µg/ml and 1 mg/ml (0, 0.1, 1, 10, 100 and 1,000 µg/ml). Cell morphology was evaluated with an optical microscope and the viability of the cells was quantitatively analyzed with a cell counting kit-8 (CCK-8) assay for up to seven days. The untreated control group exhibited normal fibroblast morphology. The shapes of the cells following 0.1, 1, 10 and 100 µg/ml A. radix treatments were similar to those of the control group. However, a significant change was noted in the 1,000 µg/ml group on day 1, when compared with the untreated group. Furthermore, on day 7, the shapes of the cells following 100 and 1,000 µg/ml A. radix treatments were rounder and fewer cells were present, when compared with those of the control group. The cultures that grew in the presence of A. radix did not exhibit any changes in the CCK?8 assay on day 2; however, significant reductions in cell viability were noticed following 100 and 1,000 µg/ml A. radix treatment on days 5 and 7. Within the limits of this study, A. radix influenced the viability of the stem cells derived from the gingiva. Thus, the direct application of A. radix to oral tissues may produce adverse effects at high doses. Therefore, the concentration and application time of A. radix requires meticulous control to obtain optimal results. These effects require consideration, if the use of A. radix is planned for the treatment of dental diseases.
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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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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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DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier.
Nature
PUBLISHED: 05-13-2014
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Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL-AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4(-/-) MLL-AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL-AF9 blasts, which requires cyclin-dependent kinase inhibitor p21(Cip1) (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia.
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Effects of chebulic acid on advanced glycation endproducts-induced collagen cross-links.
Biol. Pharm. Bull.
PUBLISHED: 04-24-2014
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Advanced glycation end-products (AGEs) have been implicated in the development of diabetic complications. We report the antiglycating activity of chebulic acid (CA), isolated from Terminalia chebula on breaking the cross-links of proteins induced by AGEs and inhibiting the formation of AGEs. Aminoguanidine (AG) reduced 50% of glycated bovine serum albumin (BSA) with glycolaldehyde (glycol-BSA)-induced cross-links of collagen at a concentration of 67.8 ± 2.5 mM, the level of CA required for exerting a similar antiglycating activity was 38.8 ± 0.5 µM. Also, the breaking activity on collagen cross-links induced by glycol-BSA was potent with CA (IC50=1.46 ± 0.05 mM), exhibiting 50-fold stronger breaking activity than with ALT-711, a well-known cross-link breaker (IC50=72.2 ± 2.4 mM). IC50 values of DPPH· scavenging activity for CA and ascorbic acid (AA) were 39.2 ± 4.9 and 19.0 ± 1.2 µg dry matter (DM) mL(-1), respectively, and ferric reducing and antioxidant power (FRAP) activities for CA and AA were 4.70 ± 0.06 and 11.4 ± 0.1 mmol/FeSO4·7H2O/g DM, respectively. The chelating activities of CA, AG and ALT711 on copper-catalyzed oxidation of AA were compared, and in increasing order, ALT-711 (IC50 of 1.92 ± 0.20 mM)
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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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ATP-citrate lyase regulates cellular senescence via AMPK- and p53-dependent pathway.
FEBS J.
PUBLISHED: 04-11-2014
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ATP citrate lyase (ACLY) is a key enzyme involved in de novo lipogenesis by catalyzing cytosolic citrate into acetyl-coA and oxaloacetate. Upregulated ACLY in various types of tumors enhances the fatty acid synthesis and supplies an excess acetyl-CoA for histone acetylation. However, some evidence showed that its enzymatic activity alone is insufficient for explaining ACLY-silencing-mediated growth arrest in tumor cells. In this study, we found that ACLY-knockdown in primary human cells triggers cellular senescence and the activation of tumor suppressor p53. Acetyl-CoA backup in ACLY-knockdown cells could not alleviate the ACLY-silencing-induced p53 activation, suggesting an independent role of ACLY activity. Instead, ACLY physically interacted with the catalytic subunit of AMPK and inhibited AMPK activity. The activation of AMPK in ACLY-knockdown conditions may lead to p53 activation, ultimately leading to cellular senescence. In cancer cells, ACLY-silencing-induced p53 activation facilitated DNA-damage-induced cell death. Taken together, we propose a novel function of ACLY in cellular senescence and tumorigenesis. This article is protected by copyright. All rights reserved.
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Evaluation of anatomical considerations in the posterior maxillae for sinus augmentation.
World J Clin Cases
PUBLISHED: 04-08-2014
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The edentulous posterior maxilla is considered a clinical challenge during dental implant treatment for many dental practitioners. This is because its insufficient bone quality, deficient alveolar ridge, spiny ridges, undercuts, and sinus pneumatization are often encountered after tooth loss. To overcome these problems, several approaches have been developed and are currently used, including sinus augmentation and bone augmentation. Today, two main procedures of sinus floor elevation for dental implant placement are in use: a two-stage technique using the lateral window approach, and a one-stage technique using a lateral or a crestal approach. In this study, we deal with the anatomic relations of the structures of the maxillary sinus during sinus augmentation. These anatomical findings can help in complications and potential injuries of the maxillary sinus procedures. It can be suggested that pre-operative evaluation is helpful for diagnosis and treatment planning and minimizing complication during the surgery.
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Egg intake during carbohydrate restriction alters peripheral blood mononuclear cell inflammation and cholesterol homeostasis in metabolic syndrome.
Nutrients
PUBLISHED: 04-08-2014
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Egg yolk contains bioactive components that improve plasma inflammatory markers and HDL profiles in metabolic syndrome (MetS) under carbohydrate restriction. We further sought to determine whether egg yolk intake affects peripheral blood mononuclear cell (PBMC) inflammation and cholesterol homeostasis in MetS, as HDL and its associated lipid transporter ATP-binding cassette transporter A1 (ABCA1) reduce the inflammatory potential of leukocytes through modulation of cellular cholesterol content and distribution. Thirty-seven men and women classified with MetS consumed a moderate carbohydrate-restricted diet (25%-30% of energy) for 12 weeks, in addition to consuming either three whole eggs per day (EGG) or the equivalent amount of yolk-free egg substitute (SUB). Interestingly, lipopolysaccharide-induced PBMC IL-1? and TNF? secretion increased from baseline to week 12 in the SUB group only, despite increases in PBMC toll-like receptor 4 (TLR4) mRNA expression in the EGG group. Compared to baseline, ABCA1 and 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression increased by week 12 in the EGG group only, whereas changes in PBMC total cholesterol positively correlated with changes in lipid raft content. Together, these findings suggest that intake of whole eggs during carbohydrate restriction alters PBMC inflammation and cholesterol homeostasis in MetS.
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Evaluation of stability after orthognathic surgery with minimal orthodontic preparation: comparison according to 3 types of fixation.
J Craniofac Surg
PUBLISHED: 03-28-2014
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This study was performed to evaluate the patterns and amount of postsurgical relapse after mandibular setback surgery with minimal orthodontic preparation. We also compared the stability of plate according to types. From January 2009 to February 2012, 26 patients (13 males, 13 females) at Seoul National University Bundang Hospital were identified. All patients underwent presurgical orthodontic treatment in less than 6 months and had mandibular setback surgery. Lateral cephalograms were taken presurgically (T0), immediately after surgery (T1), and 6 months after surgery (T2). To evaluate surgical change and surgical relapse, linear and angular measurements were performed, and results were analyzed. Comparison of the vertical and horizontal relapses between groups (group 1: sliding plate, group 2: conventional metal plate, group 3: resorbable plate) was also performed. The overall mandibular relapse was 2.80 (SD, 3.86) mm (pogonion) and 3.85 (SD, 4.44) mm (menton) anteriorly, and 1.2 (SD, 3.39) (pogonion) and 1.47 (SD, 3.48) mm (menton) superiorly. There was no significant difference among the 3 groups, however (P > 0.05). When mandibular setback surgery was performed, surgical relapse would occur anteriorly and superiorly. Significant difference can hardly be found among the 3 groups in terms of the amount of vertical and horizontal relapses.
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Development of cyclobutene- and cyclobutane-functionalized fatty acids with inhibitory activity against Mycobacterium tuberculosis.
ChemMedChem
PUBLISHED: 03-12-2014
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Eleven fatty acid analogues incorporating four-membered carbocycles (cyclobutenes, cyclobutanes, cyclobutanones, and cyclobutanols) were investigated for the ability to inhibit the growth of Mycobacterium smegmatis (Msm) and Mycobacterium tuberculosis (Mtb). A number of the analogues displayed inhibitory activity against both mycobacterial species in minimal media. Several of the molecules displayed potent levels of inhibition against Mtb, with MIC values equal to or below those observed with the anti-tuberculosis drugs D-cycloserine and isoniazid. In contrast, two of the analogues that display the greatest activity against Mtb failed to inhibit E.?coli growth under either set of conditions. Thus, the active molecules identified herein may provide the basis for the development of anti-mycobacterial agents against Mtb.
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Polyphenol-rich blackcurrant extract prevents inflammation in diet-induced obese mice.
J. Nutr. Biochem.
PUBLISHED: 03-11-2014
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Obesity is closely associated with chronic, low-grade inflammation. We investigated if polyphenol-rich blackcurrant extract (BCE) can prevent inflammation in vivo. Male C57BL/6J mice were fed a modified AIN-93M control diet containing high fat/high cholesterol (16% fat, 0.25% cholesterol by weight) or the control diet supplemented with 0.1% BCE (wt/wt) for 12 weeks. In BCE-fed mice, the percentage of body weight and adipocyte size of the epididymal fat were significantly lower than those of control mice. There were fewer crown-like structures (CLS) with concomitant decreases in F4/80, cluster of differentiation 68 and inhibitor of nuclear factor ?B kinase ? (IKK?) mRNA in the epididymal adipose of BCE-fed mice. F4/80 and IKK? mRNA levels were positively correlated with CLS number. In the skeletal muscle of mice fed with BCE, mRNA expression of genes involved in energy expenditure and mitochondrial biogenesis, including PPAR?, PPAR?, UCP-2, UCP-3 and mitochondrial transcription factor A, were significantly increased. When splenocytes from BCE-fed mice were stimulated by lipopolysaccharides, tumor necrosis factor ? and interleukin-1? mRNA were significantly lower than control splenocytes. Together, the results suggest that BCE supplementation decreases obesity-induced inflammation in adipose tissue and splenocytes, at least in part, by modulating energy metabolism in skeletal muscle.
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Upregulation of FGFR1 expression is associated with parathyroid carcinogenesis in HPT-JT syndrome due to an HRPT2 splicing mutation.
Int. J. Oncol.
PUBLISHED: 03-07-2014
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Mutations of the HRPT2 gene, which are responsible for hyperparathyroidism-jaw tumor (HPT-JT) syndrome, have been implicated in the development of a high proportion of parathyroid carcinomas. The aim of this study was to investigate differences in expression of the most important genes connected with parathyroid carcinoma between HPT-JT syndrome due to an HRPT2 splicing mutation, normal parathyroid tissue and sporadic parathyroid adenoma. Total RNAs were extracted from parathyroid carcinoma in HPT-JT syndrome harbouring HRPT2 splicing mutation or sporadic parathyroid adenoma and normal parathyroid gland, and subjected to Illumina DASL-based gene expression assay. Unsupervised hierarchical clustering analysis was used to compare gene expression in HPT-JT syndrome, sporadic parathyroid adenoma and normal parathyroid glands. We identified differentially regulated genes in HPT-JT syndrome and sporadic parathyroid adenoma relative to normal parathyroid glands using a combination of Welch's t-test and fold-change analysis. Quantitative PCR, RT-PCR and IHC were used for validation. Sixteen genes differentially regulated in the parathyroid carcinoma were associated with signal pathways, MAPK, regulation of actin cytoskeleton, prostate cancer and apoptosis. FGFR1 expression was confirmed to be significantly upregulated by validation experiments. Our gene expression profiling experiments suggest that upregulated FGFR1 expression appears to be associated with parathyroid carcinoma in HPT-JT syndrome due to an HRPT2 splicing mutation.
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Genetic structure of wild boar (Sus scrofa) populations from East Asia based on microsatellite loci analyses.
BMC Genet.
PUBLISHED: 03-04-2014
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Wild boar, Sus scrofa, is an extant wild ancestor of the domestic pig as an agro-economically important mammal. Wild boar has a worldwide distribution with its geographic origin in Southeast Asia, but genetic diversity and genetic structure of wild boar in East Asia are poorly understood. To characterize the pattern and amount of genetic variation and population structure of wild boar in East Asia, we genotyped and analyzed microsatellite loci for a total of 238 wild boar specimens from ten locations across six countries in East and Southeast Asia.
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Impact of outdoor air pollution on the incidence of tuberculosis in the Seoul metropolitan area, South Korea.
Korean J. Intern. Med.
PUBLISHED: 02-27-2014
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Although indoor air pollution is a well-known risk factor for tuberculosis (TB), the possible link between outdoor air pollution and TB development has not been examined fully. We assessed the impact of outdoor air pollution on TB development in the Seoul metropolitan area, South Korea.
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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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Neural changes associated with emotion processing in children experiencing peer rejection: a functional MRI study.
J. Korean Med. Sci.
PUBLISHED: 01-30-2014
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This study was performed to investigate differences between children who did and did not experience peer rejection in psychological state through surveys and in emotion processing during an interpersonal stress challenge task to reflect naturalistic interpersonal face-to-face relationships. A total of 20 right-handed children, 10 to 12 yr of age, completed self-rating questionnaires inquiring about peer rejection in school, depression, and anxiety. They then underwent an interpersonal stress challenge task simulating conditions of emotional stress, in reaction to positive, negative and neutral facial expression stimuli, using interpersonal feedbacks, and functional magnetic resonance imaging (FMRI) for an analysis of neural correlates during the task. Ten were the peer-rejection group, whereas the remainder were the control group. Based on the behavioral results, the peer-rejection group exhibited elevated levels of depression, state anxiety, trait anxiety and social anxiety as compared to the control group. The FMRI results revealed that the peer-rejection group exhibited greater and remarkably more extensive activation of brain regions encompassing the amygdala, orbitofrontal cortex and ventrolateral prefrontal cortex in response to negative feedback stimuli of emotional faces. The different brain reactivities characterizing emotion processing during interpersonal relationships may be present between children who do and do not experience peer rejection.
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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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Genomic variations between colistin-susceptible and -resistant Pseudomonas aeruginosa clinical isolates and their effects on colistin resistance.
J. Antimicrob. Chemother.
PUBLISHED: 01-27-2014
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The emergence of colistin-resistant Pseudomonas aeruginosa is becoming a serious concern worldwide. We investigated genetic variations involved in the acquisition and loss of colistin resistance in three clinical isogenic P. aeruginosa isolates (GKK-1, GKK-2 and GKK-3) recovered from a single patient and assessed their impacts on colistin resistance.
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Protective effect of silymarin against cisplatin-induced ototoxicity.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 01-18-2014
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Silymarin is a plant extract with strong antioxidant properties in addition to anti-inflammatory and anticarcinogenic actions. The aim of this study was to investigate the potential preventive effect of silymarin on cisplatin ototoxicity in an auditory cell line, HEI-OC1 cells.
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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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Variability of offending allergens of allergic rhinitis according to age: optimization of skin prick test allergens.
Allergy Asthma Immunol Res
PUBLISHED: 01-10-2014
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This study evaluates offending allergens in patients with allergic rhinitis (AR) according to age that establish a minimal panel for skin prick test (SPT) allergens required to identify if a patient is sensitized.
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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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The associations between immunity-related genes and breast cancer prognosis in Korean women.
PLoS ONE
PUBLISHED: 01-01-2014
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We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS) in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS) were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs) in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA). A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effects of SNPs on breast cancer prognosis. Harrell's C index was calculated to estimate the predictive accuracy of polygenic risk score model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP) was conducted to approximate the biological pathway. In addition, to confirm our results with current evidence, previous studies were systematically reviewed. Sixty-two SNPs were statistically significant at p-value less than 0.05. The most significant SNPs were rs1952438 in SOCS4 gene (hazard ratio (HR)?=?11.99, 95% CI?=?3.62-39.72, P?=?4.84E-05), rs2289278 in TSLP gene (HR?=?4.25, 95% CI?=?2.10-8.62, P?=?5.99E-05) and rs2074724 in HGF gene (HR?=?4.63, 95% CI?=?2.18-9.87, P?=?7.04E-05). In the polygenic risk score model, the HR of women in the 3rd tertile was 6.78 (95% CI?=?1.48-31.06) compared to patients in the 1st tertile of polygenic risk score. Harrell's C index was 0.813 with total patients and 0.924 in 4-fold cross validation. In the pathway analysis, 18 pathways were significantly associated with breast cancer prognosis (P<0.1). The IL-6R, IL-8, IL-10RB, IL-12A, and IL-12B was associated with the prognosis of cancer in data of both our study and a previous study. Therefore, our results suggest that genetic polymorphisms in immune-related genes have relevance to breast cancer prognosis among Korean women.
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H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation.
Elife
PUBLISHED: 12-26-2013
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Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for H3K4me1/2 on enhancers remain elusive. Furthermore, how these enzymes function on enhancers to regulate cell-type-specific gene expression is unclear. In this study, we identify MLL4 (KMT2D) as a major mammalian H3K4 mono- and di-methyltransferase with partial functional redundancy with MLL3 (KMT2C). Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of Mll4 markedly decreases H3K4me1/2, H3K27ac, Mediator and Polymerase II levels on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Together, these findings identify MLL4 as a major mammalian H3K4 mono- and di-methyltransferase essential for enhancer activation during cell differentiation. DOI: http://dx.doi.org/10.7554/eLife.01503.001.
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A randomized controlled clinical trial of two types of tapered implants on immediate loading in the posterior maxilla and mandible.
Int J Oral Maxillofac Implants
PUBLISHED: 11-27-2013
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Purpose: The aim of this study was to compare clinical outcomes and stability following immediate loading of two types of tapered implants in the partially edentulous posterior maxilla and mandible. Materials and Methods: A randomized controlled trial with 1 year of follow-up was performed on participants missing two consecutive teeth in a posterior quadrant with tapered implants with a hybrid textured surface. Group 1 received Osstem TSIII HA implants, and group 2 received Zimmer TSV implants. Group 1 implants were 4.5 or 5.0 mm in diameter, and group 2 implants were 4.7 mm in diameter; all implants were 10 mm long. Subjects received provisional restorations within 48 hours. Definitive restorations were provided 3 months (mandible) or 6 months (maxilla) later. Outcome measures were survival and success rates, marginal bone level change, implant stability quotient, and peri-implant soft tissue indices. Results: Fifty participants completed the trial (group 1: 52 implants in 26 patients; group 2: 48 implants in 24 patients). The success rates were similar-98.1% in group 1 and 97.9% in group 2-at 12 months after immediate loading, but marginal bone loss was significantly different according to the implant design. Implant stability increased significantly in both arches. There were no significant differences in soft tissue indices between implant systems. Conclusion: If high primary stability is acquired, tapered implants with hybrid textured surfaces are predictable for immediate loading in the posterior maxilla and mandible. In spite of the influence of implant design on marginal bone loss, all tapered implants showed successful clinical outcomes and stability in immediate loading.
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Enhanced performance of flexible nanocrystalline silicon thin-film solar cells using seed layers with high hydrogen dilution.
J Nanosci Nanotechnol
PUBLISHED: 11-26-2013
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Flexible hydrogenated nanocrystalline (nc-Si:H) thin-film solar cells were prepared by very high frequency plasma enhanced chemical vapor deposition (VHF-PECVD), and the effect of highly crystalline intrinsic Si seed layers at the initial growth stage of i nc-Si:H absorbers on their structural and electrical properties and on the performance of solar cells was investigated. The crystallization of i nc-Si:H absorbers was significantly enforced by the introduction of highly crystalline seed layers, resulting in the reduction of defect-dense a-Si:H grain boundary and incubation layer thickness. The open circuit voltage of the nc-Si:H solar cells with the seed layers was improved by the decrease of charged defect density in the defect-rich amorphous region.
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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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Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways.
Endocr. Relat. Cancer
PUBLISHED: 11-06-2013
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Anosmin-1, encoded by the KAL1 gene, is an extracellular matrix (ECM)-associated protein which plays essential roles in the establishment of olfactory and GNRH neurons during early brain development. Loss-of-function mutations of KAL1 results in Kallmann syndrome with delayed puberty and anosmia. There is, however, little comprehension of its role in the developed brain. As reactivation of developmental signal pathways often takes part in tumorigenesis, we investigated if anosmin-1-mediated cellular mechanisms associated with brain tumors. Our meta-analysis of gene expression profiles of patients samples and public microarray datasets indicated that KAL1 mRNA was significantly upregulated in high-grade primary brain tumors compared with the normal brain and low-grade tumors. The tumor-promoting capacity of anosmin-1 was demonstrated in the glioblastoma cell lines, where anosmin-1 enhanced cell motility and proliferation. Notably, anosmin-1 formed a part of active ?1 integrin complex, inducing downstream signaling pathways. ShRNA-mediated knockdown of anosmin-1 attenuated motility and growth of tumor cells and induced apoptosis. Anosmin-1 may also enhance the invasion of tumor cells within the ECM by modulating cell adhesion and activating extracellular proteases. In a mouse xenograft model, anosmin-1-expressing tumors grew faster, indicating the role of anosmin-1 in tumor microenvironment in vivo. Combined, these data suggest that anosmin-1 can facilitate tumor cell proliferation, migration, invasion, and survival. Therefore, although the normal function of anosmin-1 is required in the proper development of GNRH neurons, overexpression of anosmin-1 in the developed brain may be an underlying mechanism for some brain tumors.
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Configuration-controlled Au nanocluster arrays on inverse micelle nano-patterns: versatile platforms for SERS and SPR sensors.
Nanoscale
PUBLISHED: 10-24-2013
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Nanopatterned 2-dimensional Au nanocluster arrays with controlled configuration are fabricated onto reconstructed nanoporous poly(styrene-block-vinylpyridine) inverse micelle monolayer films. Near-field coupling of localized surface plasmons is studied and compared for disordered and ordered core-centered Au NC arrays. Differences in evolution of the absorption band and field enhancement upon Au nanoparticle adsorption are shown. The experimental results are found to be in good agreement with theoretical studies based on the finite-difference time-domain method and rigorous coupled-wave analysis. The realized Au nanopatterns are exploited as substrates for surface-enhanced Raman scattering and integrated into Kretschmann-type SPR sensors, based on which unprecedented SPR-coupling-type sensors are demonstrated.
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A randomised controlled trial comparing a thermal massager with artificial teardrops for the treatment of dry eye.
Br J Ophthalmol
PUBLISHED: 10-16-2013
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To evaluate the efficacy and safety of a thermal massager for the treatment of dry eye syndrome.
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Mortality of patients with obstructive sleep apnea in Korea.
J Clin Sleep Med
PUBLISHED: 10-16-2013
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Obstructive sleep apnea (OSA) is associated with diverse health risks, including death. However, the role of OSA as a risk factor for death has never been studied in Asians. This study is aimed at evaluating the influence of OSA on the mortality in Korean sleep clinic population.
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Prevalence of ocular symptoms in patients with allergic rhinitis: Korean multicenter study.
Am J Rhinol Allergy
PUBLISHED: 10-15-2013
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Allergic rhinitis (AR) is often accompanied by multiple ocular symptoms. This study aimed to evaluate the prevalence of ocular symptoms and the impact of ocular symptoms on the quality of life in patients with AR.
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Determining the applicability of threshold of toxicological concern approaches to substances found in foods.
Crit Rev Food Sci Nutr
PUBLISHED: 10-05-2013
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Threshold of Toxicological Concern (TTC) decision-support methods present a pragmatic approach to using data from well-characterized chemicals and protective estimates of exposure in a stepwise fashion to inform decisions regarding low-level exposures to chemicals for which few data exist. It is based on structural and functional categorizations of chemicals derived from decades of animal testing with a wide variety of chemicals. Expertise is required to use the TTC methods, and there are situations in which its use is clearly inappropriate or not currently supported. To facilitate proper use of the TTC, this paper describes issues to be considered by risk managers when faced with the situation of an unexpected substance in food. Case studies are provided to illustrate the implementation of these considerations, demonstrating the steps taken in deciding whether it would be appropriate to apply the TTC approach in each case. By appropriately applying the methods, employing the appropriate scientific expertise, and combining use with the conservative assumptions embedded within the derivation of the thresholds, the TTC can realize its potential to protect public health and to contribute to efficient use of resources in food safety risk management.
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RSK2-induced stress tolerance enhances cell survival signals mediated by inhibition of GSK3? activity.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-06-2013
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Our previous studies demonstrated that RSK2 plays a key role in cell proliferation and transformation induced by tumor promoters such as epidermal growth factor (EGF) in mouse and human skin cells. However, no direct evidence has been found regarding the relationship of RSK2 and cell survival. In this study, we found that RSK2 interacted and phosphorylated GSK3? at Ser9. Notably, GSK3? phosphorylation at Ser9 was suppressed in RSK2(-/-) MEFs compared with RSK2(+/+) MEFs by stimulation of EGF and calcium ionophore A23187, a cellular calcium stressor. In proliferation, we found that RSK2 deficiency suppressed cell proliferation compared with RSK2(+/+) MEFs. In contrast, GSK3?(-/-) MEFs induced the cell proliferation compared with GSK3?(+/+) MEFs. Importantly, RSK2(-/-) MEFs were induced severe cellular morphology change by A23187 and enhanced G1/G0 and sub-G1 accumulation of the cell cycle phase compared with RSK2(+/+) MEFs. The sub-G1 induction in RSK2(-/-) MEFs by A23187 was correlated with increase of cytochrome c release, caspase-3 cleavage and apoptotic DNA fragmentation compared with RSK2(+/+) MEFs. Notably, return back of RSK2 into RSK2(-/-) MEFs restored A23187-induced morphological change, and decreased apoptosis, apoptotic DNA fragmentation and caspase-3 induction compared with RSK2(-/-)/mock MEFs. Taken together, our results demonstrated that RSK2 plays an important role in stress-tolerance and cell survival, resulting in cell proliferation and cancer development.
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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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Rapid in vitro corrosion induced by crack-like pathway in biodegradable Mg-10% Ca alloy.
Microsc. Microanal.
PUBLISHED: 08-08-2013
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The in vitro corrosion mechanism of the biodegradable cast Mg-10% Ca binary alloy in Hanks solution was evaluated through transmission electron microscopy observations. The corrosion behavior depends strongly on the microstructural peculiarity of Mg?Ca phase surrounding the island-like primary Mg phase and the fast corrosion induced by the interdiffusion of O and Ca via the Mg?Ca phase of lamellar structure. At the corrosion front, we found that a nanosized crack-like pathway was formed along the interface between the Mg?Ca phase and the primary Mg phase. Through the crack-like pathway, O and Ca are atomically exchanged each other and then the corroded Mg?Ca phase was transformed to Mg oxides. The in vitro corrosion by the exchange of Ca and O at the nanosized pathway led to the rapid bulk corrosion in the Mg-Ca alloys.
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Severe Pulmonary Hypertension in Primary Sjögrens Syndrome.
Korean Circ J
PUBLISHED: 07-31-2013
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A 65 year-old female with a history of xerostomia and xerophthalmia was presented with dyspnea on exertion (New York Heart Association class III). Echocardiography and cardiac catheterization demonstrated severe pulmonary hypertension (PH). Laboratory examinations showed positive anti-nuclear and anti-Ro/SS-A antibodies. Schirmers test was positive and salivary gland scintigraphy revealed severely decreased tracer uptakes in both parotid and submandibular glands. By excluding other possible causes of PH during further examinations, she was diagnosed with severe PH associated with primary Sjögrens syndrome. Her dyspnea symptom was much improved with endothelin receptor antagonist and azathioprine.
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Comparative clinical study of three-unit fixed partial prostheses supported by two or three implants.
Int J Oral Maxillofac Implants
PUBLISHED: 07-23-2013
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To compare clinical outcomes of three-unit fixed prostheses supported by two or three implants in the posterior region.
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Alkaline pretreatment improves saccharification and ethanol yield from waste money bills.
Biosci. Biotechnol. Biochem.
PUBLISHED: 07-07-2013
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Waste money bills (WMB) is a by-product of the money making process that consists of rich-cellulosic material for many biotechnological applications. This waste money bills is unusable and usually exhausted. Saccharification was improved using various concentrations of sodium hydroxide, NaOH (0.0, 0.5, 1.0, 2.0, 2.5, and 3.0% v/v) and various reaction times (20, 30, and 40 min) during pretreatment at 121 °C. Prior to ethanol fermentation, the highest glucose yield (62.2 mg/mL) was found by pretreatment consisting of 30 min at 2.0% NaOH, and it increased 33.8% as compared to an untreated sample. The highest amount of ethanol was obtained (26.1 mg/mL) during fermentation, and this was increased 95.3 and 22.5% as compared to aerobic and anaerobic conditions respectively during pretreatment with 2.0% NaOH for 30 min. Under anaerobic conditions, ethanol fermentation was enhanced by adding 0.4 mmol benzoic acid. Production of ethanol from waste money bills would cut waste management costs and make profitable.
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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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Anesthesia for cesarean section in a patient with respiratory failure -A case report-.
Korean J Anesthesiol
PUBLISHED: 05-24-2013
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We present successful epidural anesthesia and assisted mechanical ventilation in a parturient woman with respiratory failure. A 41-year-old woman at 35 weeks of gestation was entering labor. She was pneumonectomized on the left, had bronchiectasis on the remnant lung, and was under assisted mechanical ventilation by continuous positive airway pressure (CPAP) because of severely restricted lung function and superimposed pneumonia. We administered continuous epidural analgesia for vaginal delivery, and extended it for cesarean section after failure of vaginal delivery. During the procedure, her ventilation was continuously assisted by CPAP. The maternal and fetal outcomes were successful.
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Randomized trial of the virologic response during up to two years of entecavir-adefovir combination therapy in multiple-drug-refractory chronic hepatitis B virus patients.
Antimicrob. Agents Chemother.
PUBLISHED: 05-06-2013
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A 1-year trial with entecavir plus adefovir resulted in a rate of virological response (VR) higher than that seen with lamivudine plus adefovir in multiple-drug-refractory chronic hepatitis B (CHB) patients. This extension study enrolled 89 of 90 patients who completed a 52-week randomized trial comparing treatment with entecavir plus adefovir (EA) to treatment with lamivudine plus adefovir (LA). At the baseline of the original study, all patients had lamivudine-resistant hepatitis B virus (HBV) and serum HBV DNA > 2,000 IU/ml despite prior lamivudine plus adefovir therapy. Of the 89 enrolled patients, 45 initially randomized to receive entecavir plus adefovir and the other 44 randomized to receive lamivudine plus adefovir received entecavir plus adefovir for an additional 52 weeks (EA-EA and LA-EA, respectively). The proportions of patients with a VR (serum HBV DNA < 60 IU/ml) gradually increased in both groups and were comparable at week 104 (42.2% in the EA-EA group and 34.1% in the LA-EA group; P = 0.51). The mean reductions in serum HBV DNA from baseline in the two groups were similar (-2.8 log10 IU/ml and -2.8 log10 IU/ml, respectively; P = 0.87). At week 104, the number of patients who retained the preexisting HBV mutants resistant to adefovir or entecavir had decreased from 8 to 2 in the EA-EA group and from 15 to 6 in the LA-EA group (P = 0.27). Both study groups had favorable safety profiles. In conclusion, up to 104 weeks of entecavir plus adefovir treatment was associated with a progressive VR, a decrease of levels of preexisting drug-resistant mutants, and no selection for additional resistance mutants of HBV in multiple-drug-refractory CHB patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01023217.).
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A novel wedge technique to correct the curved deviation of the cartilaginous nasal septum.
Auris Nasus Larynx
PUBLISHED: 05-05-2013
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To introduce a novel wedge technique in endonasal septoplasty to correct the curved deviation of the cartilaginous septum and describe the surgical procedure and results.
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Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea.
BMB Rep
PUBLISHED: 04-26-2013
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To understand the corneal regeneration induced by bevacizumab, we investigated the structure changes of stroma and basement membrane regeneration. A Stick soaked in 0.5 N NaOH onto the mouse cornea and 2.5 mg/ml of bevacizumab was delivered into an alkali-burned cornea (2 ?l) by subconjunctival injections at 1 hour and 4 days after injury. At 7 days after injury, basement membrane regeneration was observed by transmission electron microscope. Uneven and thin epithelial basement membrane, light density of hemidesmosomes, and edematous collagen fibril bundles are shown in the alkali-burned cornea. Injured epithelial basement membrane and hemidesmosomes and edematous collagen fibril bundles resulting from alkali-burned mouse cornea was repaired by bevacizumab treatment. This study demonstrates that bevacizumab can play an important role in wound healing in the cornea by accelerating the reestablishment of basement membrane integrity that leads to barriers for scar formation.
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Influence of torrefaction pretreatment for ethanol fermentation from waste money bills.
Biotechnol. Appl. Biochem.
PUBLISHED: 04-23-2013
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Waste money bills (WMB) that are no longer legal tender are nonrecyclable and are generally useless. In this work, we used this cellulose-rich material for ethanol fermentation for the first time. Torrefaction of this nonlignocellulosic waste material was attempted to examine whether such material could benefit from this process as a conventional lignocellulosic material does. Effects of two important parameters, that is, residence times (20, 40, and 60 Min) and temperatures (140, 160, 180, 200, and 220°C), on the torrefaction yield were studied under an inert atmosphere. Glucose and ethanol yields were compared using a factorial experimental design. The highest glucose yield (81.59 mg/mL) was obtained with a torrefaction treatment consisting of 40 min at 180 °C, and it was increased 44.89% compared to untreated WMB. Based on ethanol feasibility studies conducted on WMB, this estimated quantity of glucose could be produced for subsequent fermentation to ethanol (38.92 mg/mL) and it was increased 47.92% compared to the untreated sample. The fermentation rate was also enhanced by adding 0.4 mM benzoic acid under anaerobic conditions. It is concluded that production of ethanol from WMB would reduce waste management costs and thus would be profitable.
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Guided bone regeneration using demineralized allogenic bone matrix with calcium sulfate: case series.
J Adv Prosthodont
PUBLISHED: 04-11-2013
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The purpose of this case series was to evaluate the effect of guided bone regeneration using demineralized allogenic bone matrix with calcium sulfate.
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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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Selective advantages of two major clones of carbapenem-resistant Pseudomonas aeruginosa isolates (CC235 and CC641) from Korea: antimicrobial resistance, virulence and biofilm-forming activity.
J. Med. Microbiol.
PUBLISHED: 04-04-2013
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The characteristics of carbapenem-resistant P. aeruginosa (CRPA) isolates from Korea were investigated. Two major clones, clonal complex (CC) 235 and CC641, were identified. CC235, an important international clone, might have been imported recently in Korea as this clone displayed a homogeneous genotype, oprD mutation and antimicrobial resistance profile. While 13 ST235 isolates harboured the blaIMP-6 gene, which conferred high-level meropenem resistance, CC641 isolates showed high biofilm-forming activity. CC235 and CC641 isolates showed distinct distribution of ferripyoverdine receptor type and virulence markers. While all CC235 isolates were of the fpvAIIb type and exoS(-)/exoU(+), CC641 isolates were exoS(+)/exoU(-), and all but one showed the fpvAIII type. CC235 and CC641 isolates were also characterized by different extracellular protease activity: staphylolysin and elastase activities in CC235 and CC641, respectively. Two major CRPA clones in Korea seem to be predominant, reflecting their selective advantage by virtue of antimicrobial resistance, virulence and biofilm-forming activity.
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Risk of seizure and its clinical implication in the patients with cerebral metastasis from lung cancer.
Acta Neurochir (Wien)
PUBLISHED: 03-18-2013
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The prevalence, risk factors, and clinical implication of seizure development were investigated in patients with metastatic brain tumors.
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Diffusion and binding analyzed with combined point FRAP and FCS.
Cytometry A
PUBLISHED: 03-13-2013
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To quantify more precisely and more reliably diffusion and reaction properties of biomolecules in living cells, a novel closed description in 3D of both the bleach and the post-bleach segment of fluorescence recovery after photobleaching (FRAP) data acquired at a point, i.e., a diffraction-limited observation area, termed point FRAP, is presented. It covers a complete coupled reaction-diffusion scheme for mobile molecules undergoing transient or long-term immobilization because of binding. We assess and confirm the feasibility with numerical solutions of the differential equations. By applying this model to free EYFP expressed in HeLa cells using a customized confocal laser scanning microscope that integrates point FRAP and fluorescence correlation spectroscopy (FCS), the applicability is validated by comparison with results from FCS. We show that by taking diffusion during bleaching into consideration and/or by employing a global analysis of series of bleach times, the results can be improved significantly. As the point FRAP approach allows to obtain data with diffraction-limited positioning accuracy, diffusion and binding properties of the exon-exon junction complex (EJC) components REF2-II and Magoh are obtained at different localizations in the nucleus of MCF7 cells and refine our view on the position-dependent association of the EJC factors with a maturating mRNP complex. Our findings corroborate the concept of combining point FRAP and FCS for a better understanding of the underlying diffusion and binding processes.
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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.