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Find video protocols related to scientific articles indexed in Pubmed.
Rapid synthesis of isoquinolinones by intramolecular coupling of amides and ketones.
Org. Biomol. Chem.
PUBLISHED: 11-20-2014
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Amides and ketones were intramolecularly coupled in the presence of KOt-Bu/DMF. The reaction provided good yields of a variety of isoquinolinones. A reaction mechanism of radical addition and subsequent E2-elimination is proposed.
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Notch1 mutations are drivers of oral tumorigenesis.
Cancer Prev Res (Phila)
PUBLISHED: 11-20-2014
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Disruption of NOTCH1 signaling was recently discovered in head and neck cancer. This study aims to evaluate NOTCH1 alterations in the progression of oral squamous cell carcinoma (OSCC) and compare the occurrence of these mutations in Chinese and Caucasian populations. We used a high-throughput-PCR-based enrichment technology and next generation sequencing (NGS) to sequence NOTCH1 in 144 samples collected in China. Forty nine samples were normal oral mucosa from patients undergoing oral surgery, 45 were oral leukoplakia biopsies and 50 were chemoradiation naïve OSCC samples with 22 paired-normal tissues from the adjacent unaffected areas. NOTCH1 mutations were found in 54% of primary OSCC and 60% of pre-malignant lesions. Importantly, almost 60% of leukoplakia patients with mutated NOTCH1 carried mutations that were also identified in OSCC, indicating an important role of these clonal events in the progression of early neoplasms. We then compared all known NOTCH1 mutations identified in Chinese OSCC patients with those reported in Caucasians to date. Although we found obvious overlaps in critical regulatory NOTCH1 domains alterations and identified specific mutations shared by both groups, possible gain-of-function mutations were predominantly seen in Chinese population. Our findings demonstrate that pre-malignant lesions display NOTCH1 mutations at an early stage and are thus bona fide drivers of OSCC progression. Moreover, our results reveal that NOTCH1 promotes distinct tumorigenic mechanisms in patients from different ethnical populations.
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Combinatorial regulation of a signal-dependent activator by phosphorylation and acetylation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-19-2014
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In the fasted state, increases in catecholamine signaling promote adipocyte function via the protein kinase A-mediated phosphorylation of cyclic AMP response element binding protein (CREB). CREB activity is further up-regulated in obesity, despite reductions in catecholamine signaling, where it contributes to the development of insulin resistance. Here we show that obesity promotes the CREB binding protein (CBP)-mediated acetylation of CREB at Lys136 in adipose. Under lean conditions, CREB acetylation was low due to an association with the energy-sensing NAD(+)-dependent deacetylase SirT1; amounts of acetylated CREB were increased in obesity, when SirT1 undergoes proteolytic degradation. Whereas CREB phosphorylation stimulated an association with the KIX domain of CBP, Lys136 acetylation triggered an interaction with the CBP bromodomain (BRD) that augmented recruitment of this coactivator to the promoter. Indeed, coincident Ser133 phosphorylation and Lys136 acetylation of CREB stimulated the formation of a ternary complex with the KIX and BRD domains of CBP by NMR analysis. As disruption of the CREB:BRD complex with a CBP-specific BRD inhibitor blocked effects of CREB acetylation on target gene expression, our results demonstrate how changes in nutrient status modulate cellular gene expression in response to hormonal signals.
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5,7-dihydroxy-4'-methoxyisoflavone induces apoptosis by inhibiting the ERK and Akt pathways in human osteosarcoma cells.
Connect. Tissue Res.
PUBLISHED: 11-04-2014
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Abstract Phytoestrogens are known to prevent tumor progression by inhibiting proliferation and inducing apoptosis in cancer cells. This study aimed to determine the effect of 5,7-dihydroxy-4'-methoxyisoflavone, a phytoestrogen, on proliferation and apoptosis in the human osteosarcoma cell line U2OS. 5,7-dihydroxy-4'-methoxyisoflavone dose-dependently inhibited proliferation in U2OS cells, which was accompanied by an increase of early apoptotic cells. However, 5,7-dihydroxy-4'-methoxyisoflavone had little effect on the growth and apoptosis of normal HSF cells. This may indicate that 5,7-dihydroxy-4'-methoxyisoflavone can selectively inhibit the proliferation of cancerous cells. Meanwhile, 5,7-dihydroxy-4'-methoxyisoflavone decreased the protein levels of phosphorylated ERK and Akt. Inactivation of these pathways was confirmed by an upregulation of Bax expression and downregulation of Bcl-2 expression. Phosphorylated Akt protein levels were decreased in HSF cells only at a high concentration (80 ?M) of 5,7-dihydroxy-4'-methoxyisoflavone. Taken together, we suggest that 5,7-dihydroxy-4'-methoxyisoflavone promotes cell death of human osteosarcoma cells U2OS by induction of apoptosis, which is associated with inhibition of ERK and Akt signaling. Thus 5,7-dihydroxy-4'-methoxyisoflavone may have less toxicity to normal tissue and could be a potential therapy for osteosarcoma.
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The relationship between anthropometric indices and type 2 diabetes mellitus among adults in north-east China.
Public Health Nutr
PUBLISHED: 11-01-2014
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The present study was performed to test the predictive value of different cut-off points of anthropometric parameters for the presence of type 2 diabetes (T2DM) or glucose tolerance abnormalities in north-east Chinese adults.
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Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer.
Mol. Cancer Ther.
PUBLISHED: 10-15-2014
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JAK/STAT3 is one of the major signaling pathways that is aberrantly activated in ovarian cancer and associated with tumor progression and poor prognosis in ovarian cancer patients. In this study, we evaluated the therapeutic potential of targeting JAK/STAT3 signaling in ovarian cancer using a peritoneal dissemination mouse model. We developed this mouse model by injecting a metastatic human ovarian cancer cell line, SKOV3-M-Luc, into the peritoneal cavity of immunodeficient mice. This model displayed a phenotype similar to late stage ovarian cancer, including extensive peritoneal metastasis and ascites production. The constitutive activation of STAT3 in human ovarian cancer cells appeared to be mediated by an autocrine-cytokine loop involving the IL-6 family of cytokines and JAK1 kinase. shRNA-mediated knockdown of JAK1 or STAT3 in ovarian cancer cells led to reduced tumor growth, decreased peritoneal dissemination and diminished ascites production, suggesting a critical role of STAT3 in ovarian cancer progression. Similar results were obtained when a small-molecule inhibitor (JAKi) of the JAK1 kinase was used to treat ovarian cancer in this model. In addition, we found that the expression level of IL-6 was correlated with activation of STAT3 in ovarian cancer cells both in vitro and in vivo, suggesting a potential application of IL-6 as a biomarker. Altogether, our results demonstrate that targeting JAK1/STAT3, using shRNA knockdown or a small molecule inhibitor, effectively suppressed ovarian tumor progression and, therefore, could be a potential novel therapeutic approach for treating advanced ovarian cancer.
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Effect of CYP2C9, CYP4F2 and VKORC1 genetic polymorphisms on pharmacokinetics and pharmacodynamics of mean daily maintenance dose of warfarin in Chinese patients.
Blood Coagul. Fibrinolysis
PUBLISHED: 10-12-2014
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In this study, we studied the effects of different genetic variants of CYP2C9, VKORC1 and CYP4F2, and clinical factors on the concentration levels of S-WF, R-WF and S, R-7-OH-WF, as well as the mean daily maintenance dose of warfarin in 211 patients on warfarin therapy for at least 3 months. The genotypes of single nucleotide polymorphism (SNP), CYP2C9, VKORC1 1173C>T and CYP4F2 were identified by PCR. Plasma concentrations of S-WF and R-WF and S-7-OH-WF R-7-OH-WF were determined by HPLC-MS/MS on chiral columns. The warfarin dosage requirement correlated negatively with age and was in direct proportion to body weight. VKORC1 1173CC carrier had significantly lower dosage requirements than that with the heterozygous VKORC1 1173CT genotype. The concentration of both 7-OH-S-WF and 7-OH-R-WF, and the warfarin dose showed a significant difference. There were significant differences in the concentrations of S-WF and 7-OH-S-WF among the CYP2C9 variants. The concentration of warfarin, 7-OH-WF and warfarin maintenance dose were not affected by the CYP4F2 V433M variant. In conclusion, VKORC1 1173C>T genotype correlates strongly with a lower daily warfarin dose and the concentration of S-7-OH, R-7-OH warfarin in Han Shanghainese patients. In addition, the results not only demonstrated the effect on pharmacodynamics of warfarin, but also enhanced the enzymatic activity of CYP450 to influence the pharmacokinetic of warfarin.
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[Effects related to experiences of famine during early life on diabetes mellitus and impaired fasting glucose during adulthood].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 10-09-2014
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To investigate the effects of famine-experience during early life on diabetes mellitus and impaired fasting glucose in the adulthood.
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Facile synthesis of a mesoporous Co3O4 network for Li-storage via thermal decomposition of an amorphous metal complex.
Nanoscale
PUBLISHED: 09-25-2014
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A facile strategy is developed for mass fabrication of porous Co3O4 networks via the thermal decomposition of an amorphous cobalt-based complex. At a low mass loading, the achieved porous Co3O4 network exhibits excellent performance for lithium storage, which has a high capacity of 587 mA h g(-1) after 500 cycles at a current density of 1000 mA g(-1).
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Presepsin as a novel sepsis biomarker.
World J Emerg Med
PUBLISHED: 09-13-2014
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In 2004, a new biomarker sCD14-subtypes (presepsin) was found and its value was shown in the diagnosis and evaluation of sepsis. This article is a brief overview of the new biomarker.
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Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats.
Chem. Biol. Interact.
PUBLISHED: 08-26-2014
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Pogostemonis Herba is an important Chinese medicine widely used in the treatment of gastrointestinal dysfunction. Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major active constituent of Pogostemonis Herba. This study aimed to investigate the possible anti-ulcerogenic potential of PA and the underlying mechanism against ethanol, indomethacin and water immersion restraint-induced gastric ulcers in rats. Gross and histological gastric lesions, biochemical and immunological parameters were taken into consideration. The gastric mucus content and the antisecretory activity were analyzed through pylorus ligature model in rats. Results indicated that oral administration with PA significantly reduced the ulcer areas induced by ethanol, indomethacin and water immersion restraint. PA pretreatment significantly promoted gastric prostaglandin E2 (PGE2) and non-protein sulfhydryl group (NP-SH) levels, upregulated the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mRNA expression, and considerably boosted the gastric blood flow (GBF) and gastric mucus production in comparison with vehicle. In addition, PA modulated the levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-? (TNF-?). The levels of glutathione (GSH), catalase (CAT) and malonaldehyde (MDA) were also restored by PA. However, the gastric secretion parameters (pH, volume of gastric juice and pepsin) did not show any significant alteration. These findings suggest that PA exhibited significant gastroprotective effects against gastric ulceration. The underlying mechanisms might involve the stimulation of COX-mediated PGE2, improvement of antioxidant and anti-inflammatory status, preservation of GBF and NP-SH, as well as boost of gastric mucus production.
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Correlation analysis between central corneal thickness and intraocular pressure in juveniles in Northern China: the Jinan city eye study.
PLoS ONE
PUBLISHED: 08-22-2014
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To determine the distributions and relation of central corneal thickness (CCT) and intraocular pressure (IOP) by NT-530P in Chinese juveniles, and the effect of gender, age, height, weight and refractive errors on the CTT and IOP.
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White matter integrity and late-life depression in community-dwelling individuals: diffusion tensor imaging study using tract-based spatial statistics.
Br J Psychiatry
PUBLISHED: 08-21-2014
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Late-life depression has been associated with white matter changes in studies using the regions of interest approach.
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Association of the miR-149 Rs2292832 Polymorphism with Papillary Thyroid Cancer Risk and Clinicopathologic Characteristics in a Chinese Population.
Int J Mol Sci
PUBLISHED: 08-14-2014
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(1) Background: The genetic predisposition to papillary thyroid cancer (PTC) is far from clearly elucidated. Rs2292832 is a genetic polymorphism that located in the precursor of mir-149 and has been studied in diverse cancers. Thus far, the role of rs2292832 in PTC tumorigenesis and progression was unclear; (2) Method: Rs2292832 was genotyped in 838 PTCs, 495 patients with thyroid benign tumors (BNs) and 1006 controls in a Chinese Han population. Clinicopathological data was collected and compared. The expression level of mature mir-149 was examined in 55 normal thyroid tissue samples; (3) Results: The CC genotype of rs2292832 was significantly associated with an increased risk of PTC compared with TT homozygote (OR = 1.60, 95% CI: 1.72-2.20, p = 0.003) and TT/TC combined genotype (OR = 1.54, 95% CI: 1.14-2.09, p = 0.005). Rs2292832 is an independent risk factor correlated with tumor invasion (p = 0.006) and higher T stage in PTC patients (p = 0.007), but uncorrelated with short-term disease persistence of PTC. PTC subjects carrying CC genotype have lower mir-149-5p expression than those with TC genotype (p = 0.002). Twelve predicted target genes have been identified by collaboratively using computational tools; (4) Conclusion: Rs2292832 was possibly involved in the susceptibility and local progression of PTC in Chinese patients, by altering the expression level of mir-149-5p and its target genes.
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Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib.
Cancer
PUBLISHED: 08-07-2014
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The feasibility of monitoring epidermal growth factor receptor (EGFR) mutations in plasma DNA from patients with advanced non-small cell lung cancer (NSCLC) during treatment with erlotinib and its relation to disease progression was investigated.
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Association study of single nucleotide polymorphisms in mature microRNAs and the risk of thyroid tumor in a Chinese population.
Endocrine
PUBLISHED: 08-05-2014
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MicroRNAs (miRNAs) are small non-coding RNA molecules that are involved in a variety of cellular functions. Single nucleotide polymorphisms (SNPs) have been identified in mature miRNAs (mmSNPs), some of which have been linked to cancer risk; however, it is unclear which mmSNPs contribute to the susceptibility to thyroid tumors. In the present study, we examined the influence of selected mmSNPs on the risk of thyroid tumor. After systematic in silico screening, seventeen mmSNPs were identified and genotyped in a Chinese population including 828 patients with papillary thyroid cancer (PTC), 488 patients with benign thyroid tumor (BN), and 1038 cancer-free controls. Multivariate logistic regression analyses were conducted to evaluate the association of SNP genotypes and alleles with the risk of developing PTC and BN. Three SNPs (rs67106263 in mir-3144, GA versus GG, OR = 1.35, 1.09-1.68; rs4919510 in mir-608, CC versus GG/GC, OR = 0.76, 0.60-0.97; and rs79402775 in mir-933, AA versus GG/GA, OR = 1.76, 1.00-3.12) were associated with PTC risk. A combined effect of unfavorable genotypes was observed to give increased PTC risk in a dose-dependent manner. In addition, three SNPs (rs10061133 in mir-449b, rs79402775 in mir-933 and rs4919510 in mir-608) showed at least borderline correlations with the risk of BN. False-positive report probability was assessed for significant findings. The rs67106263 SNP was associated with the expression level of mir-3144 in thyroid tissue. These results indicate that mmSNPs may contribute to genetic susceptibility to thyroid tumors. Large validation and functional studies are required to further explore the role of mmSNPs in carcinogenesis.
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Chemosensitivity of resistant colon cancer cell lines to lobaplatin, heptaplatin, and dicycloplatin.
Int J Clin Pharmacol Ther
PUBLISHED: 07-31-2014
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Lobaplatin, heptaplatin, and dicycloplatin are three new platinum drugs. The aim of this study is to investigate the chemosensitivity of resistant colon cancer cell lines to these three drugs.
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Inducing effect of dihydroartemisinic acid in the biosynthesis of artemisinins with cultured cells of Artemisia annua by enhancing the expression of genes.
ScientificWorldJournal
PUBLISHED: 07-17-2014
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Artemisinin has been used in the production of "artemisinin combination therapies" for the treatment of malaria. Feeding of precursors has been proven to be one of the most effective methods to enhance artemisinin production in plant cultured cells. At the current paper, the biosynthesis of artemisinin (ART) and its four analogs from dihydroartemisinic acid (DHAA) in suspension-cultured cells of Artemisia annua were investigated. ARTs were detected by HPLC/GC-MS and isolated by various chromatography methods. The structures of four DHAA metabolites, namely, dihydro-epi-deoxyarteannuin B, arteannuin I, arteannuin K, and 3-?-hydroxy-dihydro-epi-deoxyarteannuin B, were elucidated by physicochemical and spectroscopic analyses. The correlation between gene expression and ART content was investigated. The results of RT-PCR showed that DHAA could up-regulate expression of amorpha-4,11-diene synthase gene (ADS), amorpha-4,11-diene C-12 oxidase gene (CYP71AV1), and farnesyl diphosphate synthase gene (FPS) (3.19-, 7.21-, and 2.04-fold higher than those of control group, resp.), which indicated that biosynthesis processes from DHAA to ART were enzyme-mediated.
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Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells.
Oncol. Rep.
PUBLISHED: 06-11-2014
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Chemokine C-C motif ligand 5 (CCL5) is an important marker related to the progression of breast cancer and is upregulated in cancer cells. However, the mechanism of the overexpression of CCL5 in tumours has not yet been clarified. The present study aimed to investigate the role of endoplasmic reticulum (ER) stress in regulating CCL5 expression and its relationship with signal transducer and activator of transcription 3 (STAT3). Meanwhile, the effect of tunicamycin, a classical ER stress inducer, and CCL5 on the transmigration of human breast cancer MCF-7 cells was observed and analysed. Compared with the normal breast epithelial tissues, expression levels of CCL5, STAT3 and CHOP, an indicator of ER stress, were significantly upregulated in breast cancer tissues. In human breast cancer MCF-7 cells, ER stress activator tunicamycin increased the expression of CCL5, STAT3 and CHOP in a time- and concentration-dependent manner. Moreover, tunicamycin-induced CCL5 expression was positively related to upregulation of unphosphorylated STAT3 (U-STAT3) but negatively related to STAT3 phosphorylation at the Tyr705 site. Furthermore, ER stress inhibited CCL5 secretion and transmigration of MCF-7 cells. This study also showed that extracellular rhCCL5 induced transmigration of MCF-7 cells which was partially blocked by the CCR5 monoclonal antibody, while knockdown of endogenous expression of CCL5 did not affect the transmigration of the cells. In conclusion, ER stress induced endogenous expression of CCL5 via elevating U-STAT3 expression; however, ER stress inhibited CCL5 secretion, which in turn, decreased the transmigration of breast cancer MCF-7 cells.
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Detection of the Three Gorges Dam influence on the Changjiang (Yangtze River) submerged delta.
Sci Rep
PUBLISHED: 05-09-2014
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While most large river-deltas in the world are facing the risk of subsidence and erosion in the Anthropocene, it is suspected that the Changjiang submerged delta (CSD) could be subjected to the impacts of the world's largest dam, the Three Gorges Dam (TGD). Here we firstly indicate that the CSD went through high accumulation (1958-1978); slight accumulation (1978-1997), slight erosion (1997-2002); and high accumulation (2002-2009), despite the 70% reduction of the sediment load from upstream since the operation of the TGD in 2003. Meanwhile, at the depocenter of the submerged delta, the accumulation maintained a high rate of 10?cm/yr during 1958-2009. This suggests on a longer term, the distal sediment source from the upstream had little effect on the CSD. Within this time frame the changes in the partition of sediment load among the branching channels of the Changjiang Estuary could likely control the shifting of the depocenter of the CSD on a decadal time scale. Episodic extreme floods and storm surges also increased the magnitude of deposition and erosion of the CSD on short-term scales. A re-evaluation of the impacts of TGD on the CSD is urgently needed.
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Analysis on minimally invasive diagnosis and treatment of 49 cases with solitary nodular ground-glass opacity.
J Thorac Dis
PUBLISHED: 04-21-2014
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This study is designed to investigate the treatment approach and prognosis of pulmonary ground-glass-like shadow, especially solitary nodular ground-glass opacity (SNGGO).
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Cap-assisted clip closure of large esophageal perforations caused by a duodenoscope during endoscopic retrograde cholangiopancreatography (with video).
Surg Laparosc Endosc Percutan Tech
PUBLISHED: 04-09-2014
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Esophageal perforation is a rare complication of endoscopic retrograde cholangiopancreatography and the perforation is usually too large to close with endoclips. We developed an endoscopic procedure for the perforations.
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Beam wander of an Airy beam with a spiral phase.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 04-04-2014
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Beam wander of an Airy beam with a spiral phase in turbulence is investigated. Using the Wigner distribution function, analytical expressions for the second-order moments and second central moments of an Airy beam with a spiral phase in turbulence are derived. A general expression of the beam wander for an Airy beam with a spiral phase is obtained. Based on the derived formula, various factors that impact on the beam wander are illustrated numerically. The results show that increasing the topological charge and the characteristic scale, or decreasing the exponential truncation factor, can be used to decrease the beam wander.
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VER-155008, a small molecule inhibitor of HSP70 with potent anti-cancer activity on lung cancer cell lines.
Exp. Biol. Med. (Maywood)
PUBLISHED: 03-27-2014
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Lung cancer is the most common malignancy and exhibits significant morbidity and mortality worldwide. Among all lung cancer subtypes, non-small-cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Although there have been intensive investigations on the underlying mechanism of NSCLC development and progression, the exact molecular basis is not well understood. Further insights on important molecular regulators of lung cancer are needed for development of novel therapeutics. The heat shock protein (HSP) family is a group of molecular chaperones that assist in protein folding, modification, and transportation. Different HSPs are essential for tumor cell survival by binding diverse client proteins and regulating homeostasis. In the current study, we sought to characterize HSP70 and HSP90 as potent regulators of NSCLC growth. Our results indicate that differential expression of HSP70 is associated with the malignant phenotype of NSCLC cell lines and plays an important regulatory role in NSCLC cell proliferation. Moreover, a specific inhibitor of HSP70, VER-155008 significantly inhibits NSCLC proliferation and cell cycle progression. We showed that this effect is largely abolished by HSP70 overexpression, indicating that the inhibitory effect of VER-155008 on cell growth is specifically through HSP70 inhibition. In addition, 17-AAD, an inhibitor of HSP90, exerts a potent synergistic effect on NSCLC proliferation with VER-155008. We also observed that inhibition of HSP70 by VER-155008 can sensitize A549 cells to ionizing radiation. These data provide proof-of-principle that VER-155008 can be a good candidate for NSCLC treatment and HSP machinery is a good target for developing NSCLC therapeutics.
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Quantitative description of the self-healing ability of a beam.
Opt Express
PUBLISHED: 03-26-2014
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Quantitative description of the self-healing ability of a beam is very important for studying or comparing the self-healing ability of different beams. As describing the similarity by using the angle of two infinite-dimensional complex vectors in Hilbert space, the angle of two intensity profiles is proposed to quantitatively describe the self-healing ability of different beams. As a special case, quantitative description of the self-healing ability of a Bessel-Gaussian beam is studied. Results show that the angle of two intensity profiles can be used to describe the self-healing ability of arbitrary beams as the reconstruction distance for quantitatively describing the self-healing ability of Bessel beam. It offers a new method for studying or comparing the self-healing ability of different beams.
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Progression of cognitive impairment in stroke/TIA patients over 3?years.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 03-21-2014
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To examine how cognitive deficits progress in the years following a stroke or transient ischaemic attack (TIA).
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Renin-angiotensin system genetic polymorphisms and brain white matter lesions in older Australians.
Am. J. Hypertens.
PUBLISHED: 03-12-2014
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White matter lesions (WMLs), seen as hyperintensities on T2-weighted magnetic resonance imaging brain scans, are common in the brains of healthy older individuals. They are thought to be related to cerebral small vessel disease and to have a genetic component to their aetiology, and hypertension is thought to be an important risk factor. Genetic polymorphisms in hypertension-related genes may therefore be associated with the formation of WMLs.
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Risk of malignancy in focal thyroid lesions identified by (18)F-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography: evidence from a large series of studies.
Tumour Biol.
PUBLISHED: 02-28-2014
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Focal thyroid incidentaloma identified on (18)F-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography ((18)F-FDG PET or PET/CT) indicates a high risk of thyroid malignancy. A meta-analysis was performed to investigate whether the maximum standardized uptake value (SUVmax) could discriminate between benign and malignant tissues in focal lesions and to explore the cutoff value of SUVmax for the diagnosis of malignancy. A total of 29 studies were involved in this meta-analysis. The results indicated that there was no statistically significant difference in the size of the two benign and malignant groups when measured by ultrasonography (95 % confidence interval (CI), -0.79 to 0.03 min; p=0.07), while a significantly higher focal SUVmax was observed in the malignant group (95 % CI, 0.34 to 1.05; p=0.0001). In conclusion, the findings of this meta-analysis suggest that a higher focal (18)F-FDG SUVmax was associated with a higher risk of thyroid malignancy, especially at a threshold of 3.3 or more.
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A universal lateral flow biosensor for proteins and DNAs based on the conformational change of hairpin oligonucleotide and its use for logic gate operations.
Biosens Bioelectron
PUBLISHED: 02-25-2014
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A universal lateral flow biosensor for proteins and DNAs was designed on the base of target-induced conformational changes of hairpin oligonucleotide (HO). CEA (carcinoembryonic antigen) protein and c-DNA were detected both with the naked eye and a strip reader. The scheme of detecting proteins and DNAs were based on the unique molecular recognition properties of HO to the targets to form different quantities of "active" biotin groups on the surface of gold nanoparticles (AuNPs). The output of the strip is the color of the test line, which inspired us to combine strip biosensor with logic gate. Two strip logic gates ("OR" and "INH") were designed in our paper and the combinatorial logic gates in our paper could be used to make high-throughput judgment about what targets were present in the input samples according to the output results. The biosensor facilitates a portable analysis at ambient temperature as it is simple to be conducted and no requirement of training is needed. The strip logic system is proved an excellent selection and can operate effectively as well as in human serum samples. Therefore, we indicate that such logic strips a foreseeable promise in application of intelligent point-of-care and in-field diagnostics.
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MicroRNA-155 in oral squamous cell carcinoma: Overexpression, localization, and prognostic potential.
Head Neck
PUBLISHED: 02-25-2014
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Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. MicroRNAs (miRNAs) play an important role in cancer, but their role in OSCC is not clarified.
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Stereo and region-selective biosynthesis of two new dihydroartemisinic acid glycosides by suspension-cultured cells of Artemisia annua.
Pharmacogn Mag
PUBLISHED: 02-21-2014
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The system of plant-cultured cells is one of the optimal systems to investigate biosynthesis pathway and their bioactive intermediates.
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Sub-cortical infarcts and the risk of falls in older people: combined results of TASCOG and Sydney MAS studies.
Int J Stroke
PUBLISHED: 02-19-2014
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White matter hyperintensities increase the risk of multiple falls in older people, but the effect of sub-cortical infarcts is unknown.
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Characterization of ambient ozone and its precursors around a coking plant.
Environ Monit Assess
PUBLISHED: 02-07-2014
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The local-scale relationship between ambient ozone (O3) and its precursors was examined around a coking plant in northern China. The upwind, plant boundary, and downwind locations were selected for investigation during the summer and autumn seasons in 2012. It was found that propene, toluene, and benzene were the top three non-methane hydrocarbon (NMHC) species for O3 formation at plant boundary, while propene, toluene, and m/p-xylene were the top three NMHC species at downwind location. Isoprene was the dominant species for O3 formation at upwind location. It was also found that an O3 depressing process occurred at plant boundary as a result of high NO emissions. Both local photochemistry and transport led to O3 accumulation at the downwind locations. The variation of NMHC concentration during O3 polluted and non-polluted episodes was investigated, and it indicated that NMHC concentration was higher during non-polluted episodes than polluted episodes. The impacts of precursors on O3 formation under different meteorological conditions were also examined.
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A facile solution route to deposit TiO2 nanowire arrays on arbitrary substrates.
Nanoscale
PUBLISHED: 02-04-2014
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A facile solution-based technique was developed to grow vertically aligned TiO2 nanowires with predominantly anatase phase on arbitrary substrates of stainless steel, glass, silicon wafer and carbon cloth at the low temperature of 80 °C and in an open atmosphere.
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The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.
Age (Dordr)
PUBLISHED: 01-09-2014
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Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n?=?880) and brain volumes by magnetic resonance imaging (n?=?312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0?±?4.2 vs. 46.7?±?5.7 mm(3) vs. 18.1?±?6.2, respectively, p?
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The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.
Paul M Thompson, Jason L Stein, Sarah E Medland, Derrek P Hibar, Alejandro Arias Vasquez, Miguel E Rentería, Roberto Toro, Neda Jahanshad, Gunter Schumann, Barbara Franke, Margaret J Wright, Nicholas G Martin, Ingrid Agartz, Martin Alda, Saud Alhusaini, Laura Almasy, Jorge Almeida, Kathryn Alpert, Nancy C Andreasen, Ole A Andreassen, Liana G Apostolova, Katja Appel, Nicola J Armstrong, Benjamin Aribisala, Mark E Bastin, Michael Bauer, Carrie E Bearden, Orjan Bergmann, Elisabeth B Binder, John Blangero, Henry J Bockholt, Erlend Bøen, Catherine Bois, Dorret I Boomsma, Tom Booth, Ian J Bowman, Janita Bralten, Rachel M Brouwer, Han G Brunner, David G Brohawn, Randy L Buckner, Jan Buitelaar, Kazima Bulayeva, Juan R Bustillo, Vince D Calhoun, Dara M Cannon, Rita M Cantor, Melanie A Carless, Xavier Caseras, Gianpiero L Cavalleri, M Mallar Chakravarty, Kiki D Chang, Christopher R K Ching, Andrea Christoforou, Sven Cichon, Vincent P Clark, Patricia Conrod, Giovanni Coppola, Benedicto Crespo-Facorro, Joanne E Curran, Michael Czisch, Ian J Deary, Eco J C de Geus, Anouk den Braber, Giuseppe Delvecchio, Chantal Depondt, Lieuwe de Haan, Greig I de Zubicaray, Danai Dima, Rali Dimitrova, Srdjan Djurovic, Hongwei Dong, Gary Donohoe, Ravindranath Duggirala, Thomas D Dyer, Stefan Ehrlich, Carl Johan Ekman, Torbjørn Elvsåshagen, Louise Emsell, Susanne Erk, Thomas Espeseth, Jesen Fagerness, Scott Fears, Iryna Fedko, Guillén Fernández, Simon E Fisher, Tatiana Foroud, Peter T Fox, Clyde Francks, Sophia Frangou, Eva Maria Frey, Thomas Frodl, Vincent Frouin, Hugh Garavan, Sudheer Giddaluru, David C Glahn, Beata Godlewska, Rita Z Goldstein, Randy L Gollub, Hans J Grabe, Oliver Grimm, Oliver Gruber, Tulio Guadalupe, Raquel E Gur, Ruben C Gur, Harald H H Göring, Saskia Hagenaars, Tomáš Hájek, Geoffrey B Hall, Jeremy Hall, John Hardy, Catharina A Hartman, Johanna Hass, Sean N Hatton, Unn K Haukvik, Katrin Hegenscheid, Andreas Heinz, Ian B Hickie, Beng-Choon Ho, David Hoehn, Pieter J Hoekstra, Marisa Hollinshead, Avram J Holmes, Georg Homuth, Martine Hoogman, L Elliot Hong, Norbert Hosten, Jouke-Jan Hottenga, Hilleke E Hulshoff Pol, Kristy S Hwang, Clifford R Jack, Mark Jenkinson, Caroline Johnston, Erik G Jönsson, René S Kahn, Dalia Kasperaviciute, Sinead Kelly, Sungeun Kim, Peter Kochunov, Laura Koenders, Bernd Krämer, John B J Kwok, Jim Lagopoulos, Gonzalo Laje, Mikael Landén, Bennett A Landman, John Lauriello, Stephen M Lawrie, Phil H Lee, Stephanie Le Hellard, Herve Lemaitre, Cassandra D Leonardo, Chiang-Shan Li, Benny Liberg, David C Liewald, Xinmin Liu, Lorna M Lopez, Eva Loth, Anbarasu Lourdusamy, Michelle Luciano, Fabio Macciardi, Marise W J Machielsen, Glenda M Macqueen, Ulrik F Malt, René Mandl, Dara S Manoach, Jean-Luc Martinot, Mar Matarin, Karen A Mather, Manuel Mattheisen, Morten Mattingsdal, Andreas Meyer-Lindenberg, Colm McDonald, Andrew M McIntosh, Francis J McMahon, Katie L McMahon, Eva Meisenzahl, Ingrid Melle, Yuri Milaneschi, Sebastian Mohnke, Grant W Montgomery, Derek W Morris, Eric K Moses, Bryon A Mueller, Susana Muñoz Maniega, Thomas W Mühleisen, Bertram Müller-Myhsok, Benson Mwangi, Matthias Nauck, Kwangsik Nho, Thomas E Nichols, Lars-Göran Nilsson, Allison C Nugent, Lars Nyberg, Rene L Olvera, Jaap Oosterlaan, Roel A Ophoff, Massimo Pandolfo, Melina Papalampropoulou-Tsiridou, Martina Papmeyer, Tomas Paus, Zdenka Pausova, Godfrey D Pearlson, Brenda W Penninx, Charles P Peterson, Andrea Pfennig, Mary Phillips, G Bruce Pike, Jean-Baptiste Poline, Steven G Potkin, Benno Pütz, Adaikalavan Ramasamy, Jerod Rasmussen, Marcella Rietschel, Mark Rijpkema, Shannon L Risacher, Joshua L Roffman, Roberto Roiz-Santiañez, Nina Romanczuk-Seiferth, Emma J Rose, Natalie A Royle, Dan Rujescu, Mina Ryten, Perminder S Sachdev, Alireza Salami, Theodore D Satterthwaite, Jonathan Savitz, Andrew J Saykin, Cathy Scanlon, Lianne Schmaal, Hugo G Schnack, Andrew J Schork, S Charles Schulz, Remmelt Schür, Larry Seidman, Li Shen, Jody M Shoemaker, Andrew Simmons, Sanjay M Sisodiya, Colin Smith, Jordan W Smoller, Jair C Soares, Scott R Sponheim, Emma Sprooten, John M Starr, Vidar M Steen, Stephen Strakowski, Lachlan Strike, Jessika Sussmann, Philipp G Sämann, Alexander Teumer, Arthur W Toga, Diana Tordesillas-Gutierrez, Daniah Trabzuni, Sarah Trost, Jessica Turner, Martijn van den Heuvel, Nic J van der Wee, Kristel van Eijk, Theo G M van Erp, Neeltje E M van Haren, Dennis van 't Ent, Marie-José van Tol, Maria C Valdés Hernández, Dick J Veltman, Amelia Versace, Henry Völzke, Robert Walker, Henrik Walter, Lei Wang, Joanna M Wardlaw, Michael E Weale, Michael W Weiner, Wei Wen, Lars T Westlye, Heather C Whalley, Christopher D Whelan, Tonya White, Anderson M Winkler, Katharina Wittfeld, Girma Woldehawariat, Christiane Wolf, David Zilles, Marcel P Zwiers, Anbupalam Thalamuthu, Peter R Schofield, Nelson B Freimer, Natalia S Lawrence, Wayne Drevets, .
Brain Imaging Behav
PUBLISHED: 01-09-2014
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The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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Distinct and concurrent pathways of Pol II- and Pol IV-dependent siRNA biogenesis at a repetitive trans-silencer locus in Arabidopsis thaliana.
Plant J.
PUBLISHED: 01-06-2014
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Short interfering RNAs (siRNAs) homologous to transcriptional regulatory regions can induce RNA-directed DNA methylation (RdDM) and transcriptional gene silencing (TGS) of target genes. In our system, siRNAs are produced by transcribing an inverted DNA repeat (IR) of enhancer sequences, yielding a hairpin RNA that is processed by several Dicer activities into siRNAs of 21-24 nt. Primarily 24-nt siRNAs trigger RdDM of the target enhancer in trans and TGS of a downstream GFP reporter gene. We analyzed siRNA accumulation from two different structural forms of a trans-silencer locus in which tandem repeats are embedded in the enhancer IR and distinguished distinct RNA polymerase II (Pol II)- and Pol IV-dependent pathways of siRNA biogenesis. At the original silencer locus, Pol-II transcription of the IR from a 35S promoter produces a hairpin RNA that is diced into abundant siRNAs of 21-24 nt. A silencer variant lacking the 35S promoter revealed a normally masked Pol IV-dependent pathway that produces low levels of 24-nt siRNAs from the tandem repeats. Both pathways operate concurrently at the original silencer locus. siRNAs accrue only from specific regions of the enhancer and embedded tandem repeat. Analysis of these sequences and endogenous tandem repeats producing siRNAs revealed the preferential accumulation of siRNAs at GC-rich regions containing methylated CG dinucleotides. In addition to supporting a correlation between base composition, DNA methylation and siRNA accumulation, our results highlight the complexity of siRNA biogenesis at repetitive loci and show that Pol II and Pol IV use different promoters to transcribe the same template.
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Long noncoding RNA GHET1 promotes the development of bladder cancer.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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In spite of the advances in the diagnosis and treatment of bladder cancer, the prognosis of bladder cancer remains relatively poor. As a result, it is vital to identify novel diagnostic and prognostic marker of bladder cancer. A growing volume of literature has implicated the vital role of long noncoding RNA in the development of cancer. GHET1, a recently identified lncRNA, was initially characterized in gastric cancer. However, its role in bladder cancer remains largely unknown. In this study, we demonstrated that GHET1 was upregulated in bladder cancer tissues compared to adjacent normal tissues and its over-expression correlates with tumor size, advanced tumor and lymph node status, and poor survival. GHET1 knockdown suppressed the proliferation and invasion of bladder cancer cells in vitro. In the meantime, inhibition of GHET1 reversed the epithelial-mesenchymal-transition in bladder cancer cell line. Taken together, our study suggests that the potential use of GHET1 as a prognostic marker and therapeutic target of bladder cancer.
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A comprehensive resource of genomic, epigenomic and transcriptomic sequencing data for the black truffle Tuber melanosporum.
Gigascience
PUBLISHED: 01-01-2014
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Tuber melanosporum, also known in the gastronomic community as "truffle", features one of the largest fungal genomes (125 Mb) with an exceptionally high transposable element (TE) and repetitive DNA content (>58%). The main purpose of DNA methylation in fungi is TE silencing. As obligate outcrossing organisms, truffles are bound to a sexual mode of propagation, which together with TEs is thought to represent a major force driving the evolution of DNA methylation. Thus, it was of interest to examine if and how T. melanosporum exploits DNA methylation to maintain genome integrity.
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Novel ThickNet features for the discrimination of amnestic MCI subtypes.
Neuroimage Clin
PUBLISHED: 01-01-2014
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Amnestic mild cognitive impairment (aMCI) is considered to be a transitional stage between healthy aging and Alzheimer's disease (AD), and consists of two subtypes: single-domain aMCI (sd-aMCI) and multi-domain aMCI (md-aMCI). Individuals with md-aMCI are found to exhibit higher risk of conversion to AD. Accurate discrimination among aMCI subtypes (sd- or md-aMCI) and controls could assist in predicting future decline.
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IFIM: a database of integrated fitness information for microbial genes.
Database (Oxford)
PUBLISHED: 01-01-2014
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Knowledge of an organism's fitness for survival is important for a complete understanding of microbial genetics and effective drug design. Current essential gene databases provide only binary essentiality data from genome-wide experiments. We therefore developed a new database that Integrates quantitative Fitness Information for Microbial genes (IFIM). The IFIM database currently contains data from 16 experiments and 2186 theoretical predictions. The highly significant correlation between the experiment-derived fitness data and our computational simulations demonstrated that the computer-generated predictions were often as reliable as the experimental data. The data in IFIM can be accessed easily, and the interface allows users to browse through the gene fitness information that it contains. IFIM is the first resource that allows easy access to fitness data of microbial genes. We believe this database will contribute to a better understanding of microbial genetics and will be useful in designing drugs to resist microbial pathogens, especially when experimental data are unavailable. Database URL: http://cefg.uestc.edu.cn/ifim/ or http://cefg.cn/ifim/
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The Sub-Classification of Amnestic Mild Cognitive Impairment Using MRI-Based Cortical Thickness Measures.
Front Neurol
PUBLISHED: 01-01-2014
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Amnestic mild cognitive impairment (aMCI) is considered to be the transitional stage between healthy aging and Alzheimer's disease (AD). Moreover, aMCI individuals with additional impairment in one or more non-memory cognitive domains are at higher risk of conversion to AD. Hence accurate identification of the sub-types of aMCI would enable earlier detection of individuals progressing to AD.
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An experimental study of using Chai Lai Prescription to treat in vitro rabbit models of reflux esophagitis.
Chin. Med. J.
PUBLISHED: 11-30-2013
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Chai Lai Prescription is a Chinese herbal compound which is used to sooth the liver, strengthen the spleen and harmonize the stomach for descending adverse Qi. We initiated the study to investigate its mechanism of treating in vitro rabbit reflux esophagitis models.
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Intramolecular Dehydrative Coupling of Tertiary Amines and Ketones Promoted by KO-t-Bu/DMF: A New Synthesis of Indole Derivatives.
Org. Lett.
PUBLISHED: 11-20-2013
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A new synthesis of indole derivatives has been achieved through intramolecular dehydrative coupling of tertiary amines and ketones promoted by KO-t-Bu/DMF. The reaction probably proceeds via an ?-amino alkyl radical pathway.
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MLS-2384, a new 6-bromoindirubin derivative with dual JAK/Src kinase inhibitory activity, suppresses growth of diverse cancer cells.
Cancer Biol. Ther.
PUBLISHED: 11-01-2013
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Janus kinase (JAK) and Src kinase are the two major tyrosine kinase families upstream of signal transducer and activator of transcription (STAT). Among the seven STAT family proteins, STAT3 is constitutively activated in many diverse cancers. Upon activation, JAK and Src kinases phosphorylate STAT3, and thereby promote cell growth and survival. MLS-2384 is a novel 6-bromoindirubin derivative with a bromo-group at the 6-position on one indole ring and a hydrophilic group at the 3-position on the other indole ring. In this study, we investigated the kinase inhibitory activity and anticancer activity of MLS-2384. Our data from in vitro kinase assays, cell viability analyses, Western blotting analyses and animal model studies, demonstrate that MLS-2384 is a dual JAK/Src kinase inhibitor, and suppresses growth of various human cancer cells, such as prostate, breast, skin, ovarian, lung and liver. Consistent with the inactivation of JAK and Src kinases, phosphorylation of STAT3 was inhibited in a dose-dependent manner in the cancer cells treated with MLS-2384. STAT3 downstream proteins involved in cell proliferation and survival, such as c-Myc and Mcl-1, are down-regulated by MLS-2384 in prostate cancer cells, whereas Survivin is down-regulated in A2058 cells. In these two cancer cell lines, PARP is cleaved, indicating that MLS-2384 induces apoptosis in human melanoma and prostate cancer cells. Importantly, MLS-2384 suppresses tumor growth with low toxicity in a mouse xenograft model of human melanoma. Taken together, MLS-2384 demonstrates dual JAK/Src inhibitory activity and suppresses tumor cell growth both in vitro and in vivo. Our findings support further development of MLS-2384 as a potential small-molecule therapeutic agent that targets JAK, Src and STAT3 signaling in multiple human cancer cells.
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Laser sintered porous polycaprolacone scaffolds loaded with hyaluronic acid and gelatin-grafted thermoresponsive hydrogel for cartilage tissue engineering.
Biomed Mater Eng
PUBLISHED: 10-30-2013
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The aim of this study is to evaluate a soft/hard bi-phase scaffold for cartilage tissue engineering. Chondrocyte proliferation, glycoaminoglycan production and total collagen content are compared between laser-sintered porous polycaprolactone (PCL) scaffolds with and without a thermoresponsive hydrogel grafted with hyaluronic acid and gelatin. The in vitro results show that scaffolds loaded with hydrogel have a higher initial chondrocyte attachment than PCL scaffolds. At day 21 and 28, scaffolds loaded with hydrogel have a significantly higher glycosaminoglycan (GAG) production than PCL scaffolds alone, and total collagen content including collagen type II in the hydrogel-loaded group is three times higher than the group without hydrogel. It is concluded that the laser-sintered porous PCL scaffold has good cytocompatibility, and that the hydrogel phase is able to enhance initial chondrocytes attachment as well as GAG and collagen production of chondrocytes. This study suggests that a soft/hard bi-phase scaffold may be used for cartilage tissue engineering to enhance in vitro chondrogenesis.
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GeneOptimizer program-assisted cDNA reengineering enhances sRAGE autologous expression in Chinese hamster ovary cells.
Protein Expr. Purif.
PUBLISHED: 10-19-2013
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Soluble receptor for advanced glycation end products (sRAGE) is a secreted mammalian protein that functions as a decoy to counter-react RAGE signaling-resultant pathological conditions, and has high therapeutic potentials. Our prior studies showed that recombinant human sRAGE expressed in Chinese hamster, Ceanothus griseus, ovary (CHO) cells is modified by specific N-glycosylation, and exhibits higher bioactivity than that expressed in other host systems including insect Spodoptera frugiperda cells. Here, we show that GeneOptimizer software program-assisted, reengineered sRAGE cDNA enhances the recombinant protein expression in CHO cells. The cDNA sequence encoding human sRAGE was optimized for RNA structure, stability, and codon usages in CHO cells. We found that such optimization augmented sRAGE expression over 2 folds of its wild-type counterpart. We also studied how individual parameter impacted sRAGE autologous expression in CHO cells, and whether sRAGE bioactivity was compromised. We found that the enhanced expression appeared not to affect sRAGE N-glycosylation and bioactivity. Optimization of sRAGE expression provides a basis for future large-scale production of this protein to meet medical needs.
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Efficient cyclization of tertiary amines and alkenes promoted by KOt-Bu-DMF.
Chem. Commun. (Camb.)
PUBLISHED: 10-18-2013
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Nitrogen heterocycles could be prepared in good yields via intramolecular cyclization of tertiary amines and alkenes promoted by KOt-Bu-DMF.
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Novel electrochemical aptamer biosensor based on an enzyme-gold nanoparticle dual label for the ultrasensitive detection of epithelial tumour marker MUC1.
Biosens Bioelectron
PUBLISHED: 08-28-2013
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A novel platform based on a hairpin oligonucleotide (HO) switch, gold nanoparticles (AuNPs), and enzyme signal amplification for the ultrasensitive detection of mucin 1 protein (MUC1) was developed in this assay. This HO aptamers and horseradish peroxidase (HRP) were immobilised on the AuNPs to yield HO-AuNP-HRP conjugates. AuNPs were used as labels and bridges between the HO and HRP. HRP was also used as label for catalysing the oxidation of o-phenylenediamine by H2O2. The reaction product was 2,3-diaminophenazine (DAP), which was reduced and could be detected at surface of modified electrode. The reduction signal of DAP was used as a probe for the sensitive detection. After the recognition between oligonucleotide and MUC1, biotin was exposed. Biotin, along with the conjugate, was captured by streptavidin onto the surface of modified electrode. Therefore, the detection of target MUC1 which was a membrane-associated glycoprotein of the mucin family could be sensitively transduced via detection of the electrochemical reduction signal of DAP. Compared to other aptasensors, this biosensor has a good linear correlation ranges from 8.8nM to 353.3nM and a lower detection limit of 2.2nM for MUC1. The proposed method provided a new electrochemical approach for the detection of MUC1.
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Utility of intraindividual reaction time variability to predict white matter hyperintensities: a potential assessment tool for clinical contexts?
J Int Neuropsychol Soc
PUBLISHED: 08-08-2013
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Intraindividual variability (IIV) refers to reaction time (RT) variation across the trials of a given cognitive task. Little research has contrasted different measures of IIV or assessed how many RT trials are required to provide a robust measure of the construct. We, therefore, investigated three measures of IIV (raw SD, coefficient of variation, and intraindividual SD statistically removing time-on-task effects) in relation to frontal white matter hyperintensities (obtained through structural MRI) in 415 cognitively normal community-dwelling adults aged 44 to 48 years. Results indicated the three IIV measures did not differ greatly in predictions of white matter hyperintensities, although it is possible that time-on-task effects were influential. As few as 20 trials taking approximately 52 s to administer provided a reliable prediction of frontal white matter hyperintensities. We conclude that future work should evaluate the comparative utility of different IIV measures in relation to persons exhibiting clear neuropathology.
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Influence of fuel mass load, oxygen supply and burning rate on emission factor and size distribution of carbonaceous particulate matter from indoor corn straw burning.
J Environ Sci (China)
PUBLISHED: 08-08-2013
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The uncertainty in emission estimation is strongly associated with the variation in emission factor (EF), which could be influenced by a variety of factors such as fuel properties, stove type, fire management and even methods used in measurements. The impacts of these factors are complicated and often interact with each other. Controlled burning experiments were conducted to investigate the influences of fuel mass load, air supply and burning rate on the emissions and size distributions of carbonaceous particulate matter (PM) from indoor corn straw burning in a cooking stove. The results showed that the EFs of PM (EF(PM)), organic carbon (EFoc) and elemental carbon (EF(EC)) were independent of the fuel mass load. The differences among them under different burning rates or air supply amounts were also found to be insignificant (p > 0.05) in the tested circumstances. PM from the indoor corn straw burning was dominated by fine PM with diameter less than 2.1 microm, contributing 86.4% +/- 3.9% of the total. The size distribution of PM was influenced by the burning rate and air supply conditions. On average, EF(PM), EF(OC) and EF(EC) for corn straw burned in a residential cooking stove were (3.84 +/- 1.02), (0.846 +/- 0.895) and (0.391 +/- 0.350) g/kg, respectively. EF(PM), EF(OC) and EF(EC) were found to be positively correlated with each other (p < 0.05), but they were not significantly correlated with the EF of co-emitted CO, suggesting that special attention should be paid to the use of CO as a surrogate for other incomplete combustion pollutants.
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Confirmation of papillary thyroid cancer susceptibility loci identified by genome-wide association studies of chromosomes 14q13, 9q22, 2q35 and 8p12 in a Chinese population.
J. Med. Genet.
PUBLISHED: 07-11-2013
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Five single nucleotide polymorphisms (SNPs) were previously reported to be associated with thyroid cancer in European populations in two genome-wide association studies (GWAS): rs965513 (9q22.33), rs944289 (14q13.3), rs116909374 (14q13.3), rs966423 (2q35) and rs2439302 (8p12). Only the first two SNPs have been validated in independent populations and none were replicated in Chinese populations.
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Enhancement of vindoline and vinblastine production in suspension-cultured cells of Catharanthus roseus by artemisinic acid elicitation.
World J. Microbiol. Biotechnol.
PUBLISHED: 07-10-2013
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Elicitation is an important strategy to improve production of secondary metabolites in vitro. Artemisinic acid was studied as a novel elicitor to enhance the yield of terpenoid indole alkaloids in the present paper. Our results demonstrated that the concentrations of vindoline and vinblastine were increased by sixfold and twofold, respectively, compared to those of the control group after treatment with artemisinic acid. To elucidate the underlying mechanism, we investigated the gene expression of four enzymes involved in the biosynthetic pathway of vinblastine in the suspension-cultured cells of Catharanthu sroseus. RT-PCR experiment showed that artemisinic acid was able to up-regulate the transcriptions of tryptophan decarboxylase, geraniol 10-hydroxylase, tabersonine 16-hydroxylase and deacetoxyvindoline 4-hydroxylase.
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The heritability of volumes of brain structures and its relationship to age: A review of twin and family studies.
Ageing Res. Rev.
PUBLISHED: 07-05-2013
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Total brain volume (BV) and the volumes of brain substructures are influenced by genes, the magnitude of which changes with age. One approach to the examination of genetic influences on the volumes of brain structures is to determine their heritability using twin and family studies. We reviewed published cross-sectional studies which examined heritability in healthy subjects at different ages. We identified 32 studies, which examined a total of 77 brain volumetric measures. The findings of our review showed that BVs are under significant genetic influence at all ages, although different brain regions showed different heritability levels. Furthermore, the cross-sectional approach of our review found that heritability factor for the majority of BVs declined with age, such as in the total brain and cerebrum, followed by subsequent increment of environmental influences. Overall, this study identified for the first time a cross-sectional pattern for brain structures heritability changes with age, and suggests the potential for longitudinal investigations in the future.
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Biosynthesis pathways of ginkgolides.
Pharmacogn Rev
PUBLISHED: 06-01-2013
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The ginkgolides, acting as anti-platelet-activating factors, have been studied for many years. The biosynthetic pathway of ginkgolides is still far away from unveiling at the level of molecular genetics and biochemistry. There are at least 11 kinds of enzymes having been cloned from Ginkgo biloba L., which catalyze the formation of ginkgolides via a series of reactions. Some researchers have indicated that the addition of precursors and elicitors can influence the accumulation of ginkgolides in the suspension cell cultures of G. biloba. There are also other factors that can influence the production of ginkgolides. This review focuses on the aforementioned aspects to discuss the biosynthetic pathways of the ginkgolides.
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Limited relationships between two-year changes in sulcal morphology and other common neuroimaging indices in the elderly.
Neuroimage
PUBLISHED: 05-16-2013
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Measuring the geometry or morphology of sulcal folds has recently become an important approach to investigating neuroanatomy. However, relationships between cortical sulci and other brain structures are poorly understood. The present study investigates how age-related changes in sulcal width are associated with age-related changes in traditional indices of brain structure such as cortical thickness, and cortical gray matter (GM), white matter (WM), subcortical, and white matter hyperintensity (WMH) volumes. These indices and sulcal width were measured at baseline and at two-year follow up in 185 community-dwelling individuals (91 men) aged 70-89 years. There were significant increases in sulcal width and WMH volume, and significant decreases in all other indices between baseline and follow-up. Sulcal widening was associated with decreases in cortical GM, subcortical and WM volumes. A further association between sulcal width and cortical thickness became non-significant when cortical GM volume was controlled for. Our findings give insights into the mechanisms responsible for cortical sulcal morphology. The relationships between sulcal morphology and other common measures suggest that it could be a more comprehensive measure for clinical classifications than traditional neuroimaging metrics, such as cortical thickness.
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PRMT5 modulates the metabolic response to fasting signals.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-13-2013
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Under fasting conditions, increases in circulating glucagon maintain glucose balance by promoting hepatic gluconeogenesis. Triggering of the cAMP pathway stimulates gluconeogenic gene expression through the PKA-mediated phosphorylation of the cAMP response element binding (CREB) protein and via the dephosphorylation of the latent cytoplasmic CREB regulated transcriptional coactivator 2 (CRTC2). CREB and CRTC2 activities are increased in insulin resistance, in which they promote hyperglycemia because of constitutive induction of the gluconeogenic program. The extent to which CREB and CRTC2 are coordinately up-regulated in response to glucagon, however, remains unclear. Here we show that, following its activation, CRTC2 enhances CREB phosphorylation through an association with the protein arginine methyltransferase 5 (PRMT5). In turn, PRMT5 was found to stimulate CREB phosphorylation via increases in histone H3 Arg2 methylation that enhanced chromatin accessibility at gluconeogenic promoters. Because depletion of PRMT5 lowers hepatic glucose production and gluconeogenic gene expression, these results demonstrate how a chromatin-modifying enzyme regulates a metabolic program through epigenetic changes that impact the phosphorylation of a transcription factor in response to hormonal stimuli.
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Unprecedented Construction of C?C Double Bonds via Ir-Catalyzed Dehydrogenative and Dehydrative Cross-Couplings.
Org. Lett.
PUBLISHED: 04-26-2013
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Unprecedented constructions of C?C double bonds have been achieved by Ir-catalyzed intramolecular dehydrogenative and dehydrative cross-coupling of tertiary amines and ketones. The reactions are proposed to proceed via an Ir-mediated C-H activation mechanism.
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The N-glycoform of sRAGE is the key determinant for its therapeutic efficacy to attenuate injury-elicited arterial inflammation and neointimal growth.
J. Mol. Med.
PUBLISHED: 04-24-2013
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Signaling of the receptor for advanced glycation end products (RAGE) has been implicated in the development of injury-elicited vascular complications. Soluble RAGE (sRAGE) acts as a decoy of RAGE and has been used to treat pathological vascular conditions in animal models. However, previous studies used a high dose of sRAGE produced in insect Sf9 cells (sRAGE(Sf9))and multiple injections to achieve the therapeutic outcome. Here, we explore whether modulation of sRAGE N-glycoform impacts its bioactivity and augments its therapeutic efficacy. We first profiled carbohydrate components of sRAGE produced in Chinese hamster Ovary cells (sRAGE(CHO)) to show that a majority of its N-glycans belong to sialylated complex types that are not shared by sRAGE(Sf9). In cell-based NF-?B activation and vascular smooth muscle cell (VSMC) migration assays, sRAGE(CHO) exhibited a significantly higher bioactivity relative to sRAGE(Sf9) to inhibit RAGE alarmin ligand-induced NF-?B activation and VSMC migration. We next studied whether this N-glycoform-associated bioactivity of sRAGE(CHO) is translated to higher in vivo therapeutic efficacy in a rat carotid artery balloon injury model. Consistent with the observed higher bioactivity in cell assays, sRAGE(CHO) significantly reduced injury-induced neointimal growth and the expression of inflammatory markers in injured vasculature. Specifically, a single dose of 3 ng/g of sRAGE(CHO) reduced neointimal hyperplasia by over 70%, whereas the same dose of sRAGE(Sf9) showed no effect. The administered sRAGE(CHO) is rapidly and specifically recruited to the injured arterial locus, suggesting that early intervention of arterial injury with sRAGE(CHO) may offset an inflammatory circuit and reduce the ensuing tissue remodeling. Our findings showed that the N-glycoform of sRAGE is the key determinant underlying its bioactivity and thus is an important glycobioengineering target to develop a highly potent therapeutic sRAGE for future clinical applications.
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Effects of triptolide on degeneration of dendritic spines induced by A?1-40 injection in rat hippocampus.
Neurol. Sci.
PUBLISHED: 03-30-2013
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Although the exact cause of Alzheimers disease (AD) remains elusive, mounting evidence continues to support the involvement of neuroinflammation in the development of AD. Triptolide isolated from the herb Tripterygium wilfordii Hook F has anti-inflammatory and immunosuppressive activities. In this study, we observed the effects of triptolide on dendritic spines of hippocampal neurons in model rats with AD. Thirty male SD rats were randomly divided into control group, AD model group and triptolide-treated group. The AD model group was made with bilateral microinjection of aggregated beta-amyloid protein (A?)1-40 into hippocampus in rats and the control group rats were injected with normal saline in the same way. The triptolide-treated group rats were administered triptolide intraperitoneally for 30 days after microinjection of aggregated A?1-40 into hippocampus. Dendritic morphology of hippocampal neurons in each group was analyzed using Golgi staining and ImageJ software. Our data showed that the total number of intersection points of dendrites and spine density in hippocampal neurons in the AD model group were decreased as compared with the control group. However, the total number of intersection points of dendrites and spine density in hippocampal neurons in the triptolide-treated group were increased as compared with the AD model group. Our results indicate that triptolide can alleviate the degeneration of dendritic spines in hippocampal neurons in model rats with AD.
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In vivo monitoring of oxidative burst on aloe under salinity stress using hemoglobin and single-walled carbon nanotubes modified carbon fiber ultramicroelectrode.
Biosens Bioelectron
PUBLISHED: 03-21-2013
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Single-walled carbon nanotubes (SWCNTs) and hemoglobin (Hb) modified carbon fiber ultramicroelectrode (CFUME) were employed to construct a direct electron transfer based in vivo H2O2 sensor. At the low working potential of -0.1 V, Hb/SWCNTs/CFUME showed a dynamic range up to 0.405 mM with a low detection limit of 4 ?M (S/N=3) and a high sensitivity of 1.07 log(A) log(M)(-1) cm(-2). The apparent Michaelis-Menten constant (Km, app) was estimated to be as low as 1.35 mM. Due to the extremely small dimension and low working potential, Hb/SWCNTs/CFUME could give directly amperometric in vivo monitoring of H2O2 in aloe leaves with salt stress for 19.5h without the requirement of complex data processing and extra surface coatings to avoid interferences. The sharp increase of H2O2 level in aloe leaves with salt stress was clearly observed using Hb/SWCNTs/CFUME from 12.5 h, while in the aloe without salt stress, H2O2 level remained stable in the whole measurement. For further confirming the in vivo response of Hb/SWCNTs/CFUME, catalase (CAT) was injected into the spot adjacent to the sensor and caused rapid current decrease, which suggests the scavenging of H2O2. These results indicate that Hb/SWCNTs/CFUME can be a powerful tool for in vivo investigation of ROS.
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Coadministration of glycogen-synthase kinase 3 inhibitor with morphine attenuates chronic morphine-induced analgesic tolerance and withdrawal syndrome.
J Chin Med Assoc
PUBLISHED: 03-19-2013
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Glycogen-synthase kinase 3 (GSK3) is involved in many signaling pathways and is associated with a host of high-profile pathophysiological states. However, its role in morphine tolerance, especially naloxone-precipitated withdrawal syndrome, has not been well investigated. The present study was undertaken to study the role of GSK3 in chronic morphine exposure.
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The Sydney Centenarian Study: methodology and profile of centenarians and near-centenarians.
Int Psychogeriatr
PUBLISHED: 03-19-2013
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The study of exceptionally long-living individuals can inform us about the determinants of successful aging. There are few population-based studies of centenarians and near-centenarians internationally, but none in Australia.
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Is Alzheimers a disease of the white matter?
Curr Opin Psychiatry
PUBLISHED: 03-16-2013
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Alzheimers disease has long been primarily considered a disease of gray matter. However, convergent evidence has suggested that white matter abnormalities are also important components of Alzheimers disease. We undertook a review of the recent findings of Alzheimers disease related white matter aberrations identified in patients with Alzheimers disease and using in-vitro and in-vivo models, and discuss the potential causes of white matter damage in Alzheimers disease. In doing so, we aim to provide a renewed insight into white matter changes in Alzheimers disease and related dementias.
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A longitudinal study of brain atrophy over two years in community-dwelling older individuals.
Neuroimage
PUBLISHED: 03-01-2013
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Most previous neuroimaging studies of age-related brain structural changes in older individuals have been cross-sectional and/or restricted to clinical samples. The present study of 345 community-dwelling non-demented individuals aged 70-90years aimed to examine age-related brain volumetric changes over two years. T1-weighted magnetic resonance imaging scans were obtained at baseline and at 2-year follow-up and analyzed using the FMRIB Software Library and FreeSurfer to investigate cortical thickness and shape and volumetric changes of subcortical structures. The results showed significant atrophy across much of the cerebral cortex with bilateral transverse temporal regions shrinking the fastest. Atrophy was also found in a number of subcortical structures, including the CA1 and subiculum subfields of the hippocampus. In some regions, such as left and right entorhinal cortices, right hippocampus and right precentral area, the rate of atrophy increased with age. Our analysis also showed that rostral middle frontal regions were thicker bilaterally in older participants, which may indicate its ability to compensate for medial temporal lobe atrophy. Compared to men, women had thicker cortical regions but greater rates of cortical atrophy. Women also had smaller subcortical structures. A longer period of education was associated with greater thickness in a number of cortical regions. Our results suggest a pattern of brain atrophy with non-demented people that resembles a less extreme form of the changes associated with Alzheimers disease (AD).
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Factors predicting reversion from mild cognitive impairment to normal cognitive functioning: a population-based study.
PLoS ONE
PUBLISHED: 02-15-2013
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Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition.
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Microstructural white matter changes, not hippocampal atrophy, detect early amnestic mild cognitive impairment.
PLoS ONE
PUBLISHED: 02-07-2013
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Alzheimers disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD.
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Heritability of brain volumes in older adults: the Older Australian Twins Study.
Neurobiol. Aging
PUBLISHED: 02-05-2013
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The relative contributions of genetic and environmental factors to brain structure change throughout the lifespan. Brain structures have been reported to be highly heritable in middle-aged individuals and younger; however, the influence of genes on brain structure is less studied in older adults. We performed a magnetic resonance imaging study of 236 older twins, with a mean age of 71.4 ± 5.7 years, to examine the heritability of 53 brain global and lobar volumetric measures. Total brain volume (63%) and other volumetric measures were moderately to highly heritable in late life, and these genetic influences tended to decrease with age, suggesting a greater influence of environmental factors as age advanced. Genetic influences were higher in men and on the left hemisphere compared with the right. In multivariate models, common genetic factors were observed for global and lobar total and gray matter volumes. This study examined the genetic contribution to 53 brain global and lobar volumetric measures in older twins for the first time, and the influence of age, sex, and laterality on these genetic contributions, which are useful information for a better understanding of the process of brain aging and helping individuals to have a healthy aging.
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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.