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Find video protocols related to scientific articles indexed in Pubmed.
Using Second-derivative Filters to Assist in Width Estimations of Size Exclusion Chromatography Signal Peaks with Static Light-scattering Detections to Obtain More Accurate Molecular Weight.
Anal Sci
PUBLISHED: 11-11-2014
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Static light-scattering (LS) detection can determine the molecular weight (MW) of polymers eluted with size-exclusion chromatography (SEC) without using any standards when the differential refraction index (RI) of solutes are obtained. On the other hand, the noisy chromatographic signal peak acquired using a static LS detector often causes difficulty in peak-width recognition. This disadvantage limits the determination accuracy and precision of the MW values. This study developed one second-order derivative filtering procedure by convolving the original LS chromatogram against the second-derivative curve of one artificial Gaussian-shape chromatographic peak to suppress the noises and to correct the baseline of the chromatogram. More accurate estimations of the chromatographic peak widths of pullulan samples were achieved to improve the MW determination accuracy. For noisy original chromatography peaks of pullulan 5 k (SNR of approximately 10), the non-ideal determination accuracy of the MW values (9.3%) is improved to -1.3% with the assistance of the filtering procedures.
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Ultrafast Transient Terahertz Conductivity of Monolayer MoS2 and WSe2 Grown by Chemical Vapor Deposition.
ACS Nano
PUBLISHED: 10-28-2014
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We have measured ultrafast charge carrier dynamics in monolayers and trilayers of the transition metal dichalcogenides MoS2 and WSe2 using a combination of time-resolved photoluminescence and terahertz spectroscopy. We recorded a photoconductivity and photoluminescence response time of just 350 fs from CVD-grown monolayer MoS2, and 1 ps from trilayer MoS2 and monolayer WSe2. Our results indicate the potential of these materials as high-speed optoelectronic materials.
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A novel fusidic acid resistance determinant, fusF, in Staphylococcus cohnii.
J. Antimicrob. Chemother.
PUBLISHED: 10-15-2014
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To determine MICs of fusidic acid for and identify genetic determinants of resistance in Staphylococcus cohnii isolates.
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Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer.
J. Natl. Cancer Inst.
PUBLISHED: 10-01-2014
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Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confidence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions.
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Early or late IL-10 blockade enhances Th1 and th17 effector responses and promotes fungal clearance in mice with cryptococcal lung infection.
J. Immunol.
PUBLISHED: 09-15-2014
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The potent immunoregulatory properties of IL-10 can counteract protective immune responses and, thereby, promote persistent infections, as evidenced by studies of cryptococcal lung infection in IL-10-deficient mice. To further investigate how IL-10 impairs fungal clearance, the current study used an established murine model of C57BL/6J mice infected with Cryptococcus neoformans strain 52D. Our results demonstrate that fungal persistence is associated with an early and sustained expression of IL-10 by lung leukocytes. To examine whether IL-10-mediated immune modulation occurs during the early or late phase of infection, assessments of fungal burden and immunophenotyping were performed on mice treated with anti-IL-10R-blocking Ab at 3, 6, and 9 d postinfection (dpi) (early phase) or at 15, 18, and 21 dpi (late phase). We found that both early and late IL-10 blockade significantly improved fungal clearance within the lung compared with isotype control treatment when assessed 35 dpi. Immunophenotyping identified that IL-10 blockade enhanced several critical effector mechanisms, including increased accumulation of CD4(+) T cells and B cells, but not CD8(+) T cells; specific increases in the total numbers of Th1 and Th17 cells; and increased accumulation and activation of CD11b(+) dendritic cells and exudate macrophages. Importantly, IL-10 blockade effectively abrogated dissemination of C. neoformans to the brain. Collectively, this study identifies early and late cellular and molecular mechanisms through which IL-10 impairs fungal clearance and highlights the therapeutic potential of IL-10 blockade in the treatment of fungal lung infections.
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Value of Primary Tumor Gene Signatures in Colon Cancer When National Quality Standards are Adhered to: Preliminary Results of an International Prospective Multicenter Trial.
Ann. Surg. Oncol.
PUBLISHED: 09-05-2014
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The purpose of this study was to determine if gene signatures are informative in colon cancer (CC) when National Quality Standards (NQS) are adhered to. Several studies have demonstrated the prognostic potential of gene signatures in primary CC. This has never been evaluated prospectively with adherence to NQS.
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Plasma PCSK9 levels are elevated with acute myocardial infarction in two independent retrospective angiographic studies.
PLoS ONE
PUBLISHED: 09-02-2014
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein (LDL) receptor. Mutations that block PCSK9 secretion reduce LDL-cholesterol and the incidence of myocardial infarction (MI). However, it remains unclear whether elevated plasma PCSK9 associates with coronary atherosclerosis (CAD) or more directly with rupture of the plaque causing MI.
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Association of Small Dense Low-density Lipoprotein Cholesterol in Type 2 Diabetics with Coronary Artery Disease.
Biomed J
PUBLISHED: 09-02-2014
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Background: The risk of coronary artery disease (CAD) increases two- to fourfold in diabetes. Small dense low-density lipoprotein (sdLDL) particles have been linked to an increased risk for CAD. In this study, we sought to compare the sdLDL cholesterol (sdLDL-C) level between the healthy control group and diabetics with CAD in the Taiwanese population. Methods: Serum specimens were collected from healthy females and males of various age groups (n = 294), type 2 diabetics (DM) without complications (n = 113), and patients having DM with CAD (DM-CAD) (n = 46). The commercial kit was used for the measurement of sdLDL-C level, which employs a simpler method. After heparin-magnesium precipitation of lipoproteins with density <1.044 g/ml, sdLDL (density = 1.044-1.063 g/ml) remained in the supernatant and this sdLDL-C was measured using an automated chemistry analyzer. Results: The sdLDL-C level was significantly higher in males than in females (p < 0.001) and there was an age effect on sdLDL-C (p < 0.001). The DM-CAD group had significantly higher sdLDL-C levels than the healthy control group (p < 0.001), but there was no statistical difference in the LDL-C level between DM-CAD group and the healthy control group. In addition, only individuals having both high LDL-C and sdLDL-C levels had a higher risk for DM-CAD, compared to those with low LDL-C levels and low sdLDL-C levels [Odds Ratio (OR) 4.97; 95% Confidence Interval (CI) 1.96-12.57; p = 0.001]. Conclusions: Our data suggest that the sdLDL-C level together with the LDL-C level are better risk assessment markers for type 2 diabetics with CAD than the LDL-C level alone.
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Zebrafish WNK lysine deficient protein kinase 1 (wnk1) affects angiogenesis associated with VEGF signaling.
PLoS ONE
PUBLISHED: 08-29-2014
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The WNK1 (WNK lysine deficient protein kinase 1) protein is a serine/threonine protein kinase with emerging roles in cancer. WNK1 causes hypertension and hyperkalemia when overexpressed and cardiovascular defects when ablated in mice. In this study, the role of Wnk1 in angiogenesis was explored using the zebrafish model. There are two zebrafish wnk1 isoforms, wnk1a and wnk1b, and both contain all the functional domains found in the human WNK1 protein. Both isoforms are expressed in the embryo at the initiation of angiogenesis and in the posterior cardinal vein (PCV), similar to fms-related tyrosine kinase 4 (flt4). Using morpholino antisense oligonucleotides against wnk1a and wnk1b, we observed that wnk1 morphants have defects in angiogenesis in the head and trunk, similar to flk1/vegfr2 morphants. Furthermore, both wnk1a and wnk1b mRNA can partially rescue the defects in vascular formation caused by flk1/vegfr2 knockdown. Mutation of the kinase domain or the Akt/PI3K phosphorylation site within wnk1 destroys this rescue capability. The rescue experiments provide evidence that wnk1 is a downstream target for Vegfr2 (vascular endothelial growth factor receptor-2) and Akt/PI3K signaling and thereby affects angiogenesis in zebrafish embryos. Furthermore, we found that knockdown of vascular endothelial growth factor receptor-2 (flk1/vegfr2) or vascular endothelial growth factor receptor-3 (flt4/vegfr3) results in a decrease in wnk1a expression, as assessed by in situ hybridization and q-RT-PCR analysis. Thus, the Vegf/Vegfr signaling pathway controls angiogenesis in zebrafish via Akt kinase-mediated phosphorylation and activation of Wnk1 as well as transcriptional regulation of wnk1 expression.
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Role of metal contacts in high-performance phototransistors based on WSe2 monolayers.
ACS Nano
PUBLISHED: 08-10-2014
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Phototransistors based on monolayer transition metal dichalcogenides (TMD) have high photosensitivity due to their direct band gap transition. However, there is a lack of understanding of the effect of metal contacts on the performance of atomically thin TMD phototransistors. Here, we fabricate phototransistors based on large-area chemical vapor deposition (CVD) tungsten diselenide (WSe2) monolayers contacted with the metals of different work function values. We found that the low Schottky-contact WSe2 phototransistors exhibit a very high photo gain (10(5)) and specific detectivity (10(14)Jones), values higher than commercial Si- and InGaAs-based photodetectors; however, the response speed is longer than 5 s in ambient air. In contrast, the high Schottky-contact phototransistors display a fast response time shorter than 23 ms, but the photo gain and specific detectivity decrease by several orders of magnitude. Moreover, the fast response speed of the high Schottky-contact devices is maintained for a few months in ambient air. This study demonstrates that the contact plays an important role in TMD phototransistors, and barrier height tuning is critical for optimizing the photoresponse and photoresponsivity.
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EWSR1-PBX3: A novel gene fusion in myoepithelial tumors.
Genes Chromosomes Cancer
PUBLISHED: 08-05-2014
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The genetics of myoepithelial tumors (ME) of soft tissue and bone have recently been investigated, with EWSR1-related gene fusions being seen in approximately half of the tumors. The fusion partners of EWSR1 so far described include POU5F1, PBX1, ZNF444 and, in a rare case, ATF1. We investigated by RNA sequencing an index case of EWSR1-rearranged ME of the tibia, lacking a known fusion partner, and identified a novel EWSR1-PBX3 fusion. The fusion was further validated by reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH). To evaluate if this is a recurrent event, an additional cohort of 22 EWSR1-rearranged ME cases lacking a fusion partner were screened by FISH for abnormalities in PBX3 gene. Thus, two additional cases were identified showing an EWSR1-PBX3 gene fusion. One of them was also intraosseous involving the ankle, while the other occurred in the soft tissue of the index finger. The morphology of the EWSR1-PBX3 fusion positive cases showed similar findings, with nests or sheets of epithelioid to spindle cells in a partially myxoid to collagenous matrix. All three cases showed expression of S100 and EMA by immunohistochemistry. In summary, we report a novel EWSR1-PBX3 gene fusion in a small subset of ME, thereby expanding the spectrum of EWSR1-related gene fusions seen in these tumors. This gene fusion seems to occur preferentially in skeletal ME, with two of the three study cases occurring in intraosseous locations. © 2014 Wiley Periodicals, Inc.
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A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: A pathologic and molecular study of 18 cases.
Genes Chromosomes Cancer
PUBLISHED: 08-05-2014
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Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue tumor exhibiting considerable morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Moreover, both SEF and LGFMS show MUC4 expression by immunohistochemistry. While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors. In contrast, recent studies pointed out that SEF harbor frequent EWSR1 rearrangements, with only a minority of cases showing FUS-CREB3L2 fusions. In an effort to further characterize the molecular characteristics of pure SEF and hybrid SEF/LGFMS lesions, we undertook a clinicopathologic, immunohistochemical and genetic analysis of a series of 10 SEF and 8 hybrid SEF/LGFMS tumors. The mortality rate was similar between the two groups, 44% within the pure SEF group and 37% in the hybrid SEF/LGFMS with a mean overall follow-up of 66 months. All but one pure SEF and all hybrid SEF/LGFMS-tested cases showed MUC4 immunoreactivity. The majority (90%) of pure SEF cases showed EWSR1 gene rearrangements by fluorescence in situ hybridization with only one case exhibiting FUS rearrangement. Of the nine EWSR1 positive cases, six cases harbored CREB3L1 break-apart, two had CREB3L2 rearrangement (a previously unreported finding) and one lacked evidence of CREB3L1/2 abnormalities. In contrast, all hybrid SEF/LGFMS tumors exhibited FUS and CREB3L2 rearrangements. These results further demarcate a relative cytogenetic dichotomy between pure SEF, often characterized by EWSR1 rearrangements, and hybrid SEF/LGFMS, harboring FUS-CREB3L2 fusion; the latter group recapitulating the genotype of LGFMS. © 2014 Wiley Periodicals, Inc.
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Monolayer MoS2 heterojunction solar cells.
ACS Nano
PUBLISHED: 07-22-2014
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We realized photovoltaic operation in large-scale MoS2 monolayers by the formation of a type-II heterojunction with p-Si. The MoS2 monolayer introduces a built-in electric field near the interface between MoS2 and p-Si to help photogenerated carrier separation. Such a heterojunction photovoltaic device achieves a power conversion efficiency of 5.23%, which is the highest efficiency among all monolayer transition-metal dichalcogenide-based solar cells. The demonstrated results of monolayer MoS2/Si-based solar cells hold the promise for integration of 2D materials with commercially available Si-based electronics in highly efficient devices.
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ZFP36-FOSB fusion defines a subset of epithelioid hemangioma with atypical features.
Genes Chromosomes Cancer
PUBLISHED: 06-20-2014
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Epithelioid hemangioma (EH) is a benign neoplasm with distinctive vasoformative features, which occasionally shows increased cellularity, cytologic atypia, and/or loco-regional aggressive growth, resulting in challenging differential diagnosis from malignant vascular neoplasms. Based on two intraosseous EH index cases with worrisome histologic features, such as the presence of necrosis, RNA sequencing was applied for possible fusion gene discovery and potential subclassification of a novel atypical EH subset. A ZFP36-FOSB fusion was detected in one case, while a WWTR1-FOSB chimeric transcript in the other, both were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). These abnormalities were then screened by FISH in 44 EH from different locations with seven additional EH revealing FOSB gene rearrangements, all except one being fused to ZFP36. Interestingly, 4/6 penile EH studied showed FOSB abnormalities. Although certain atypical histologic features were observed in the FOSB-rearranged EH, including solid growth, increased cellularity, mild to moderate nuclear pleomorphism, and necrosis in 3/9 cases, no overt sarcomatous areas were discerned to objectively separate the lesions from the fusion-negative EH. No patient has developed recurrence to date, but the follow-up was relatively limited and short to draw definitive conclusions regarding behavior. Although FOSB-rearranged EH do not show significant morphologic overlap with SERPINE1-FOSB fusion-positive pseudomyogenic hemangioendothelioma, FOSB oncogenic activation is emerging as an important event in these benign and intermediate groups of vascular tumors.
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Recombinant Derp5 allergen with ?S1-casein signal peptide secreted in murine milk protects against dust mite allergen-induced airway inflammation.
J. Dairy Sci.
PUBLISHED: 06-12-2014
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Recent advances in recombinant technology make transgenic animals that produce pharmaceutical proteins in their milk more feasible. The group 5 allergen isolated from Dermatophagoides pteronyssinus (Derp5) is one of the most important dust mite allergens in humans. The aims of this study were to develop transgenic mice that could secrete recombinant Derp5-containing milk and to demonstrate that ingesting recombinant milk protects against allergic airway inflammation. Two transgenes were constructed separately. The ?-LA-Derp5f transgene consisted of the bovine ?-lactalbumin (?-LA) promoter and full-length Derp5 cDNA. The ?-LA-CN-Derp5t transgene included the ?-LA promoter, a leader sequence of ?S1-casein (CN), and signal peptide-truncated Derp5 cDNA. Both species of transgenic mice were confirmed to have successful transgene integration and stable germline transmission. Western blot analysis of the milk obtained from the offspring of transgenic mice demonstrated that recombinant Derp5 was secreted successfully in the milk of ?LA-CN-Derp5t transgenic mice but not in that of ?LA-Derp5f transgenic mice. This study provides new evidence that transgenic mice can secrete recombinant Derp5 efficiently in milk by adding a signal peptide of ?S1-casein. The antigenic activity of recombinant Derp5 milk was demonstrated to have a protective effect against allergic airway inflammation in a murine model in which the ingestion of recombinant Derp5-containing milk was used as pretreatment.
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Functional genomics of the 9p21.3 locus for atherosclerosis: clarity or confusion?
Curr Cardiol Rep
PUBLISHED: 06-05-2014
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The 9p21.3 locus was the first to yield to genome-wide association studies (GWAS) seeking common genetic variants predisposing to increased risk of coronary artery atherosclerotic disease (CAD). The 59 single nucleotide polymorphisms that show highest association with CAD are clustered in a region 100,000 to 150,000 base pairs 5' to the cyclin-dependent kinase inhibitors CDKN2B (coding for p15(ink4b)) and CDKN2A (coding for p16(ink4a) and p14(ARF)). This region also covers the 3' end of a long noncoding RNA transcribed antisense to CDKN2B (CDKN2BAS, aka ANRIL for antisense noncoding RNA at the ink4 locus) whose expression has been linked to chromatin remodeling at the locus. Despite intensive investigation over the past 7 years, the functional significance of the 9p21.3 locus remains elusive. Other variants at this locus have been associated with glaucoma, glioma, and type 2 diabetes mellitus, diseases that implicate tissue-resident macrophages. Here, we review the evidence that genetic variants at 9p21.3 disrupt tissue-specific enhancers and propose new insights to guide future studies.
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LMO4 is required to maintain hypothalamic insulin signaling.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-15-2014
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Insulin action at the hypothalamus controls glucose homeostasis by suppressing hepatic glucose production and promoting glucose uptake by muscle. However, the mechanisms that control central insulin signaling have not been fully elucidated. Previously, we showed that LMO4 is highly expressed in hypothalamic nuclei that regulate glucose homeostasis. Here, we determined how loss of LMO4 in the hypothalamus would affect central insulin signaling and glucose homeostasis. In transgenic mice that have LMO4 in ablated in glutamatergic neurons, we found that insulin signaling is impaired in the hypothalamus as well as in peripheral tissues (liver and skeletal muscle). Impaired glucose homeostasis was associated with a markedly elevation in hypothalamic protein tyrosine phosphatase 1B (PTP1B) activity. PTP1B is a key phosphatase that terminates insulin signaling by dephosphorylating its receptor and downstream signaling molecules. Importantly, we found that administration of a selective PTP1B inhibitor Trodusquemine to the hypothalamus restored central insulin signaling and improved the response of peripheral tissues to insulin in these LMO4-deficient mice. Thus, our study reveals an essential requirement for LMO4 to modulate central insulin signaling.
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Methylation-associated gene silencing of RARB in areca carcinogens induced mouse oral squamous cell carcinoma.
Biomed Res Int
PUBLISHED: 05-07-2014
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Regarding oral squamous cell carcinoma (OSCC) development, chewing areca is known to be a strong risk factor in many Asian cultures. Therefore, we established an OSCC induced mouse model by 4-nitroquinoline-1-oxide (4-NQO), or arecoline, or both treatments, respectively. These are the main two components of the areca nut that could increase the occurrence of OSCC. We examined the effects with the noncommercial MCGI (mouse CpG islands) microarray for genome-wide screening the DNA methylation aberrant in induced OSCC mice. The microarray results showed 34 hypermethylated genes in 4-NQO plus arecoline induced OSCC mice tongue tissues. The examinations also used methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing to realize the methylation pattern in collected mouse tongue tissues and human OSCC cell lines of different grades, respectively. These results showed that retinoic acid receptor ? (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development. According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC. Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.
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A novel bubble-forming material for preparing hydrophobic-agent-loaded bubbles with theranostic functionality.
Acta Biomater
PUBLISHED: 05-03-2014
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In the present study, a new bubble-forming material (carboxymethyl hexanoyl chitosan, CHC), together with superparamagnetic iron oxide (SPIO) nanoparticles, was employed to prepare image-guided bubbles for efficiently encapsulating and delivering hydrophobic agents to kill tumor cells. The results showed that CHC could be used for preparing not only micronized bubbles (CHC/SPIO MBs) to exhibit ultrasound imaging functionality but also nanosized bubbles (CHC/SPIO NBs) to exhibit magnetic resonance T2 image contrast. It was found that the amounts of SPIO nanoparticles and hexane during preparation process were the key factors to obtaining CHC/SPIO NBs. Most importantly, under in vitro cell culture conditions with the same amount of camptothecin (CPT) and therapeutic sonication, CPT-loaded CHC/SPIO NBs demonstrated more significant transcellular delivery and cytotoxicity than free CPT. Subsequently, an intratumoral injection was proposed for the in vivo administration of hydrophobic-agent-loaded CHC/SPIO NBs. After injection, the distribution of a hydrophobic dye (DiR, an agent with near-infrared (NIR) fluorescence used as a model drug) released from the CHC/SPIO NBs was tracked by an NIR imaging technique. A significant tumor-specific accumulation was observed in the mouse that received the DiR-loaded CHC/SPIO NBs; the same was not observed in the mouse that received the free dye (without incorporating with CHC/SPIO NBs). It is expected, in the future, both the dose of the therapeutic agent administered and its side effects can be significantly lowered by using novel CHC/SPIO NBs together with local delivery (intratumoral injection), targeted imaging and enhanced cellular uptake of the drug.
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Lactoferrin protects against chemical-induced rat liver fibrosis by inhibiting stellate cell activation.
J. Dairy Sci.
PUBLISHED: 04-14-2014
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Liver diseases, which can be caused by alcohol abuse, chemical intoxication, viral hepatitis infection, and autoimmune disorders, are a significant health issue because they can develop into liver fibrosis and cirrhosis. Lactoferrin (LF), a siderophilic protein with 2 iron-binding sites, has been demonstrated to possess a multitude of biological functions, including antiinflammation, anticancer, and antimicrobial effects, as well as immunomodulatory-enhancing functions. In the current study, we induced hepatotoxicity in rats with dimethylnitrosamine (DMN) to establish a situation that would enable us to evaluate the hepatoprotective effects of LF against hepatic injury. Our results showed that DMN-induced hepatic pathological damage significantly decreased the body weight and liver index, increased the mRNA and protein levels of collagen ?-1(I) (ColI?-1) and ?-smooth muscle actin, and increased the hydroxyproline content. However, treatment with LF significantly increased body weight and liver index, decreased the mRNA and protein levels of ColI?-1 and ?-smooth muscle actin, and suppressed the hydroxyproline content when compared with the DMN-treated group. Liver histopathology also showed that low-dose LF (100mg/kg of body weight) or high-dose LF (300 mg/kg of body weight) could significantly reduce the incidences of liver lesions induced by DMN. These results suggest that the LF exhibits potent hepatoprotection against DMN-induced liver damage in rats and that the hepatoprotective effects of LF may be due to the inhibition of collagen production and to stellate cell activation.
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WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors.
J. Clin. Invest.
PUBLISHED: 03-27-2014
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About half of all melanomas harbor a mutation that results in a constitutively active BRAF kinase mutant (BRAF(V600E/K)) that can be selectively inhibited by targeted BRAF inhibitors (BRAFis). While patients treated with BRAFis initially exhibit measurable clinical improvement, the majority of patients eventually develop drug resistance and relapse. Here, we observed marked elevation of WNT5A in a subset of tumors from patients exhibiting disease progression on BRAFi therapy. WNT5A transcript and protein were also elevated in BRAFi-resistant melanoma cell lines generated by long-term in vitro treatment with BRAFi. RNAi-mediated reduction of endogenous WNT5A in melanoma decreased cell growth, increased apoptosis in response to BRAFi challenge, and decreased the activity of prosurvival AKT signaling. Conversely, overexpression of WNT5A promoted melanoma growth, tumorigenesis, and activation of AKT signaling. Similarly to WNT5A knockdown, knockdown of the WNT receptors FZD7 and RYK inhibited growth, sensitized melanoma cells to BRAFi, and reduced AKT activation. Together, these findings suggest that chronic BRAF inhibition elevates WNT5A expression, which promotes AKT signaling through FZD7 and RYK, leading to increased growth and therapeutic resistance. Furthermore, increased WNT5A expression in BRAFi-resistant melanomas correlates with a specific transcriptional signature, which identifies potential therapeutic targets to reduce clinical BRAFi resistance.
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The impact of climate factors on the prevalence of urolithiasis in Northern Taiwan.
Biomed J
PUBLISHED: 03-27-2014
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Urolithiasis is a common disease with high prevalence and recurrence. Its incidence varies in different geographic locations, and there are evidences that meteorological factors also affect urinary stone formation. The aim of this study is to analyze the effects of climate parameters on the numbers of shockwave treatments for urinary stones in our hospital, in order to understand the effects of these parameters on the prevalence of urolithiasis in northern Taiwan.
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Gemella parahaemolysans sp. nov. and Gemella taiwanensis sp. nov., isolated from human clinical specimens.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 03-24-2014
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Four Gram-staining-positive, catalase-negative, coccoid isolates, designated NTUH_1465(T), NTUH_2196, NTUH_4957 and NTUH_5572(T), were isolated from human specimens. The four isolates displayed more than 99.6% 16S rRNA gene sequence similarity with Gemella haemolysans ATCC 10379(T), and 96.7 to 98.6% similarity with Gemella sanguinis ATCC 700632(T), Gemella morbillorum ATCC 27824(T) or Gemella cuniculi CCUG 42726(T). However, phylogenetic analysis of concatenated sequences of three housekeeping genes, groEL, rpoB and recA, suggested that the four isolates were distinct from G. haemolysans ATCC 10379(T) and other species. Isolates NTUH_2196, NTUH_4957 and NTUH_5572(T) clustered together and formed a stable monophyletic clade. DNA-DNA hybridization values among strains NTUH_1465(T) and NTUH_5572(T) and their phylogenetically related neighbours were all lower than 49%. The four isolates could be distinguished from G. haemolysans and other species by phenotypic characteristics. Based on the phylogenetic and phenotypic results, two novel species Gemella parahaemolysans sp. nov. (type strain NTUH_1465(T)?=?BCRC 80365(T)?=?JCM 18067(T)) and Gemella taiwanensis sp. nov. (type strain NTUH_5572(T)?=?BCRC 80366(T)?=?JCM 18066(T)) are proposed.
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Graphene/MoS(2) heterostructures for ultrasensitive detection of DNA hybridisation.
Adv. Mater. Weinheim
PUBLISHED: 03-10-2014
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The photoluminescence signals of a graphene/MoS2 heterostructural stacking film are sensitive to environmental charges, which allows the single-base sequence-selective detection of DNA hybridization with sensitivity to the level of aM.
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Association between the hemodialysis eating index and risk factors of cardiovascular disease in hemodialysis patients.
J Ren Nutr
PUBLISHED: 02-28-2014
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In this study, a Hemodialysis Eating Index (HDEI) suitable for hemodialysis (HD) patients in Taiwan was developed based on the dietary recommendations of the U.S. National Kidney Foundation for HD patients and the Taiwanese 2011 Daily Food Guide. The HDEI was used to explore HD-associated cardiovascular disease (CVD) risk factors.
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Second harmonic generation from artificially stacked transition metal dichalcogenide twisted bilayers.
ACS Nano
PUBLISHED: 02-27-2014
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Optical second harmonic generation (SHG) is known as a sensitive probe to the crystalline symmetry of few-layer transition metal dichalcogenides (TMDs). Layer-number dependent and polarization resolved SHG have been observed for the special case of Bernal stacked few-layer TMDs, but it remains largely unexplored for structures deviated from this ideal stacking order. Here we report on the SHG from homo- and heterostructural TMD bilayers formed by artificial stacking with an arbitrary stacking angle. The SHG from the twisted bilayers is a coherent superposition of the SH fields from the individual layers, with a phase difference depending on the stacking angle. Such an interference effect is insensitive to the constituent layered materials and thus applicable to hetero-stacked bilayers. A proof-of-concept demonstration of using the SHG to probe the domain boundary and crystal polarity of mirror twins formed in chemically grown TMDs is also presented. We show here that the SHG is an efficient, sensitive, and nondestructive characterization for the stacking orientation, crystal polarity, and domain boundary of van der Waals heterostructures made of noncentrosymmetric layered materials.
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Aerosolized bovine lactoferrin reduces lung injury and fibrosis in mice exposed to hyperoxia.
Biometals
PUBLISHED: 02-26-2014
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This study investigated the ability of aerosolized bovine lactoferrin (bLF) to protect the lungs from injury induced by chronic hyperoxia. Female CD-1 mice were exposed to hyperoxia (FiO2 = 80 %) for 7 days to induce lung injury and fibrosis. The therapeutic effects of bLF, administered via an aerosol delivery system, on the chronic lung injury induced by this period of hyperoxia were measured by bronchoalveolar lavage, lung histology, cell apoptosis, and inflammatory cytokines in the lung tissues. After exposure to hyperoxia for 7 days, the survival of the mice was significantly decreased to 20 %. The protective effects of bLF against hyperoxia were further confirmed by significant reductions in lung edema, total cell numbers in bronchoalveolar lavage fluid, inflammatory cytokines (IL-1? and IL-6), pulmonary fibrosis, and apoptotic DNA fragmentation. The aerosolized bLF protected the mice from oxygen toxicity and increased the survival fraction to 66.7 % in the hyperoxic model. The results support the use of an aerosol therapy with bLF in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure or chronic obstructive pulmonary disease.
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Osteoponin promoter controlled by DNA methylation: aberrant methylation in cloned porcine genome.
Biomed Res Int
PUBLISHED: 02-24-2014
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Cloned animals usually exhibited many defects in physical characteristics or aberrant epigenetic reprogramming, especially in some important organ development. Osteoponin (OPN) is an extracellular-matrix protein involved in heart and bone development and diseases. In this study, we investigated the correlation between OPN mRNA and its promoter methylation changes by the 5-aza-dc treatment in fibroblast cell and promoter assay. Aberrant methylation of porcine OPN was frequently found in different tissues of somatic nuclear transferred cloning pigs, and bisulfite sequence data suggested that the OPN promoter region -2615 to -2239 nucleotides (nt) may be a crucial regulation DNA element. In pig ear fibroblast cell culture study, the demethylation of OPN promoter was found in dose-dependent response of 5-aza-dc treatment and followed the OPN mRNA reexpression. In cloned pig study, discrepant expression pattern was identified in several cloned pig tissues, especially in brain, heart, and ear. Promoter assay data revealed that four methylated CpG sites presenting in the -2615 to -2239 nt region cause significant downregulation of OPN promoter activity. These data suggested that methylation in the OPN promoter plays a crucial role in the regulation of OPN expression that we found in cloned pigs genome.
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Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan maternal and infant cohort study.
Environ. Health Perspect.
PUBLISHED: 02-20-2014
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Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment.
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Prenatal Exposure to Phthalate Esters and Behavioral Syndromes in Children at Eight Years of Age: Taiwan Maternal and Infant Cohort Study.
Environ. Health Perspect.
PUBLISHED: 02-18-2014
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Few studies have shown an association between prenatal phthalate exposure and adverse effects on neurodevelopment and behavior in young children.
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SPG7 variant escapes phosphorylation-regulated processing by AFG3L2, elevates mitochondrial ROS, and is associated with multiple clinical phenotypes.
Cell Rep
PUBLISHED: 02-06-2014
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Mitochondrial production of reactive oxygen species (ROS) affects many processes in health and disease. SPG7 assembles with AFG3L2 into the mAAA protease at the inner membrane of mitochondria, degrades damaged proteins, and regulates the synthesis of mitochondrial ribosomes. SPG7 is cleaved and activated by AFG3L2 upon assembly. A variant in SPG7 that replaces arginine 688 with glutamine (Q688) is associated with several phenotypes, including toxicity of chemotherapeutic agents, type 2 diabetes mellitus, and (as reported here) coronary artery disease. We demonstrate that SPG7 processing is regulated by tyrosine phosphorylation of AFG3L2. Carriers of Q688 bypass this regulation and constitutively process and activate SPG7 mAAA protease. Cells expressing Q688 produce higher ATP levels and ROS, promoting cell proliferation. Our results thus reveal an unexpected link between the phosphorylation-dependent regulation of the mitochondria mAAA protease affecting ROS production and several clinical phenotypes.
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High-volume plasma exchange in a patient with acute liver failure due to non-exertional heat stroke in a sauna.
J Clin Apher
PUBLISHED: 02-04-2014
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Heat stroke is a life-threatening condition characterized by an increased core body temperature (over 40°C) and a systemic inflammatory response, which may lead to a syndrome of multiple organ dysfunction. Heat stroke may be due to either strenuous exercise or non-exercise-induced exposure to a high environmental temperature. Current management of heat stroke is mostly supportive, with an emphasis on cooling the core body temperature and preventing the development of multiple organ dysfunction. Prognosis of heat stroke depends on the severity of organ involvement. Here, we report a rare case of non-exercise-induced heat stroke in a 73-year-old male patient who was suffering from acute liver failure after prolonged exposure in a hot sauna room. We successfully managed this patient by administering high-volume plasma exchange, and the patient recovered completely after treatment. J. Clin. Apheresis 29:281-283, 2014. © 2014 Wiley Periodicals, Inc.
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Effects of konjac glucomannan, inulin and cellulose on acute colonic responses to genotoxic azoxymethane.
Food Chem
PUBLISHED: 01-20-2014
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Mice were fed low-fibre, or that supplemented with soluble fibre (konjac glucomannan, KGM; inulin), or insoluble fibre (cellulose) to determine how these three fibres modulated the acute colonic responses to an azoxymethane (AOM) treatment. Results indicated that KGM and inulin exerted greater anti-genotoxic effects compared to cellulose and up-regulated the gene expressions of glutathione S-transferase and antioxidant enzymes. The apoptotic index in the distal colon was the greatest and the expression of Bcl-2 was the lowest in the KGM group 24h after the AOM treatment. On the other hand, the proliferative index and expression of Cyclin D1 were lower in all fibre groups. Furthermore, KGM increased cecal short-chain fatty acid contents, and both KGM and inulin increased fecal probiotic concentrations. This study suggested that soluble fibres were more effective than cellulose on ameliorating AOM-induced genotoxicity by up-regulating antioxidant enzyme genes, and enhancing epithelium apoptosis by down-regulating Bcl-2.
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Trunk Control Ability after Minimally Invasive Lumbar Fusion Surgery during the Early Postoperative Phase.
J Phys Ther Sci
PUBLISHED: 01-07-2014
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[Purpose] Lumbar fusion has been used for spinal disorders when conservative treatment fails. The minimally invasive approach causes minimal damage to the back muscles and shortens the postoperative recovery time. However, evidence regarding functional recovery in patients after minimally invasive lumbar spinal fusion is limited. The purpose of this study was to investigate how trunk control ability is affected after minimally invasive lumbar fusion surgery during the early postoperative phase. [Subjects and Methods] Sixteen patients and 16 age- and sex-matched healthy participants were recruited. Participants were asked to perform a maximum forward reaching task and were evaluated 1 day before and again 1 month after the lumbar fusion surgery. Center of pressure (COP) displacement, back muscle strength, and scores for the Visual Analog Scale, and Chinese version of the modified Oswestry Disability Index (ODI) were recorded. [Results] The healthy control group exhibited more favorable outcomes than the patient group both before and after surgery in back strength, reaching distance, reaching velocity, and COP displacement. The patient group improved significantly after surgery in all clinical outcome measurements. However, reaching distance decreased, and the reaching velocity as well as COP displacement did not differ before and after surgery. [Conclusion] The LBP patients with lumbar fusion surgery showed improvement in pain intensity 1 month after surgery but no improvement in trunk control during forward reaching. The results provide evidence that the back muscle strength was not fully recovered in patients 1 month after surgery and limited their ability to move their trunk forward.
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Ultrahigh-gain photodetectors based on atomically thin graphene-MoS2 heterostructures.
Sci Rep
PUBLISHED: 01-03-2014
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Due to its high carrier mobility, broadband absorption, and fast response time, the semi-metallic graphene is attractive for optoelectronics. Another two-dimensional semiconducting material molybdenum disulfide (MoS2) is also known as light- sensitive. Here we show that a large-area and continuous MoS2 monolayer is achievable using a CVD method and graphene is transferable onto MoS2. We demonstrate that a photodetector based on the graphene/MoS2 heterostructure is able to provide a high photogain greater than 10(8). Our experiments show that the electron-hole pairs are produced in the MoS2 layer after light absorption and subsequently separated across the layers. Contradictory to the expectation based on the conventional built-in electric field model for metal-semiconductor contacts, photoelectrons are injected into the graphene layer rather than trapped in MoS2 due to the presence of a perpendicular effective electric field caused by the combination of the built-in electric field, the applied electrostatic field, and charged impurities or adsorbates, resulting in a tuneable photoresponsivity.
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LMO4 is essential for paraventricular hypothalamic neuronal activity and calcium channel expression to prevent hyperphagia.
J. Neurosci.
PUBLISHED: 01-02-2014
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The dramatic increase in the prevalence of obesity reflects a lack of progress in combating one of the most serious health problems of this century. Recent studies have improved our understanding of the appetitive network by focusing on the paraventricular hypothalamus (PVH), a key region responsible for the homeostatic balance of food intake. Here we show that mice with PVH-specific ablation of LIM domain only 4 (Lmo4) become rapidly obese when fed regular chow due to hyperphagia rather than to reduced energy expenditure. Brain slice recording of LMO4-deficient PVH neurons showed reduced basal cellular excitability together with reduced voltage-activated Ca(2+) currents. Real-time PCR quantification revealed that LMO4 regulates the expression of Ca(2+) channels (Cacna1h, Cacna1e) that underlie neuronal excitability. By increasing neuronal activity using designer receptors exclusively activated by designer drugs technology, we could suppress food intake of PVH-specific LMO4-deficient mice. Together, these results demonstrate that reduced neural activity in LMO4-deficient PVH neurons accounts for hyperphagia. Thus, maintaining PVH activity is important to prevent hyperphagia-induced obesity.
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Sex steroid hormone levels and reproductive development of eight-year-old children following in utero and environmental exposure to phthalates.
PLoS ONE
PUBLISHED: 01-01-2014
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In utero exposure to phthalates may adversely affect reproductive development in children due to the anti-androgenic properties of the pthalates. Accordingly, we aimed to determine the effects of in utero and environmental phthalate exposure on the reproductive development of eight-year-old children. We recruited 180 children in central Taiwan during November 2001 and followed them until August 2009 when all children became eight years old. Birth outcomes were collected. Bone age, hormone concentrations, and reproductive developmental stages were determined. Phthalate metabolite levels, including mono-2-ethylhexyl phthalate [MEHP], mono-n-butyl phthalate [MnBP], and mono-benzyl phthalate [MBzP], were assessed. No significant gender differences were found in in utero phthalate exposure. Maternal urinary levels of phthalate metabolites did not correlate significantly with birth outcomes, physical characteristics, and reproductive hormones of the eight-year-old children. Regarding the urinary phthalate metabolite levels of the eight-year-old children, MEHP correlated significantly with serum progesterone levels. MEHP levels in girls correlated significantly with serum progesterone levels. MnBP correlated significantly with serum FSH in all children. In girls, MnBP correlated with serum FSH, and MBzP correlated with serum progesterone and FSH levels. Urinary phthalate metabolite levels did not correlate with female developmental stages or the development of female reproductive organs. Phthalate metabolites did not correlate with the physical characteristics and reproductive hormones in boys. Therefore, environmental exposure to phthalates, as determined by urinary phthalate metabolite levels of eight-year-old children, may affect reproductive hormone levels in children, indicating that further studies on the environmental health effects of phthalates are warranted.
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MicroRNA-328 inhibits renal tubular cell epithelial-to-mesenchymal transition by targeting the CD44 in pressure-induced renal fibrosis.
PLoS ONE
PUBLISHED: 01-01-2014
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Epithelial-mesenchymal transition (EMT) occurs in stressed tubular epithelial cells, contributing to renal fibrosis. Initial mechanisms promoting EMT are unknown. Pressure force is an important mechanism contributing to the induction and progression of renal fibrogenesis in ureteric obstruction. In our study of cultured rat renal tubular cells (NRK-52E) under 60 mmHg of pressure, we found that the epithelial marker E-cadherin decreased and mesenchymal markers, e.g., ?-smooth muscle actin, fibronectin and Snail, increased. Pressure also induced the expression of connective tissue growth factor and transforming growth factor-?. MicroRNA array assays showed that pressure reduced miR-328 at the initial stage of pressurization. We identified a potential target sequence of miR-328 in rat CD44 3'-untranslated regions. In contrast with the miR-328 expression, CD44 expression was up-regulated at the initial pressurization stage. We also found that miR-328 expression decreased and CD44 increased in ureteric obstruction kidneys in the animal study. CD44 siRNA transfection significantly increased E-cadherin expression and inhibited pressure-induced EMT. Both hyaluronan binding peptide pep-1 and osteopontin neutralizing antibody inhibited pressure-induced EMT. Our results suggest that miR-328-mediated CD44 transient upregulation is an important trigger of the pressure-induced EMT in renal fibrosis.
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FTSJ2, a heat shock-inducible mitochondrial protein, suppresses cell invasion and migration.
PLoS ONE
PUBLISHED: 01-01-2014
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Ribosomal RNA large subunit methyltransferase J (RrmJ), an Escherichia coli heat shock protein, is responsible for 2'-O-ribose methylation in 23S rRNA. In mammals, three close homologs of RrmJ have been identified and have been designated as FTSJ1, FTSJ2 and FTSJ3; however, little is known about these genes. In this study, we characterized the mammalian FTSJ2, which was the most related protein to RrmJ in a phylogenetic analysis that had similar amino acid sequence features and tertiary protein structures of RrmJ. FTSJ2 was first identified in this study as a nucleus encoded mitochondrial protein that preserves the heat shock protein character in mammals in which the mRNA expressions was increased in porcine lung tissues and A549 cells after heat shock treatment. In addition, a recent study in non-small cell lung cancer (NSCLC) suggested that the FTSJ2 gene is located in a novel oncogenic locus. However, our results demonstrate that the expression of FTSJ2 mRNA was decreased in the more invasive subline (CL1-5) of the lung adenocarcinoma cells (CL1) compared with the less invasive subline (CL1-0), and overexpression of FTSJ2 resulted in the inhibition of cell invasion and migration in the rhabdomyosarcoma cell (TE671). In conclusion, our findings indicate that mammalian FTSJ2 is a mitochondrial ortholog of E. coli RrmJ and conserves the heat shock protein properties. Moreover, FTSJ2 possesses suppressive effects on the invasion and migration of cancer cells.
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Urotensin II induces interleukin 8 expression in human umbilical vein endothelial cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Urotensin II (U-II), an 11-amino acid peptide, exerts a wide range of actions in cardiovascular systems. Interleukin-8 (IL-8) is secreted by endothelial cells, thereby enhancing endothelial cell survival, proliferation, and angiogenesis. However, the interrelationship between U-II and IL-8 as well as the detailed intracellular mechanism of U-II in vascular endothelial cells remain unclear. The aim of this study was to investigate the effect of U-II on IL-8 expression and to explore its intracellular mechanism in human umbilical vein endothelial cells.
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Identification of transforming hepatitis B virus S gene nonsense mutations derived from freely replicative viruses in hepatocellular carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
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The correlation between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) has been well-established. But the roles of viral factor remain uncertain. Only HBV X gene and nonsense mutations of S gene (C-terminal truncation of HBV surface protein) have been demonstrated to have transforming activity. Whether they play a significant role in hepatocarcinogenesis is still uncertain.
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Maternal arsenic exposure and DNA damage biomarkers, and the associations with birth outcomes in a general population from Taiwan.
PLoS ONE
PUBLISHED: 01-01-2014
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Inorganic arsenic (iAs) is an established transplacental agent known to affect fetal development in animal studies. However, iAs has not been adequately studied in the general population with respect to iAs exposure during pregnancy and its impact on the health status of newborns. The aims of this study were to 1) elucidate the association between arsenic exposure and oxidative/methylated DNA damage in pregnant women, and 2) determine the association with birth outcomes. A birth cohort study of 299 pregnant mother-newborn pairs was recruited during 2001-2002 in Taiwan. We collected maternal urine samples during the 3(rd) trimester for measuring iAs and its metabolites. We used high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for quantifications of the arsenic species. Liquid chromatography/tandem mass spectrometer (LC-MS/MS) was used to measure the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and N(7)-methylguanosine (N(7)-MeG) DNA damage biomarkers. Birth outcomes were collected to assess the associations with maternal arsenic exposure and the DNA damage biomarkers. Multiple regression analyses showed that maternal urinary iAs had positive associations with the methylated N(7)-MeG (beta?=?0.35, p<0.001) and oxidative 8-oxodG (beta?=?0.24, p<0.001) DNA damage biomarkers, and a decreased one-minute (1-min) Apgar score (beta?=?-0.23, p?=?0.041). Maternal N(7)-MeG was also associated with a decreased 1-min Apgar score (beta?=?-0.25, p?=?0.042). Mutual adjustment for iAs and N(7)-MeG showed an independent and significant prediction for a decreased 1-min Apgar score of iAs (beta?=?-0.28, p?=?0.036). Maternal iAs exposure was associated with both maternal DNA damage and adverse newborn health. Maternal N(7)-MeG levels might be a novel biomarker for monitoring fetal health related to iAs.
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Tubulin inhibitors: a patent review.
Expert Opin Ther Pat
PUBLISHED: 12-09-2013
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Introduction: Microtubules play an important role in several cellular processes, particularly in the formation of the mitotic spindle during the process of mitosis. These highly dynamic mitotic-spindle microtubules have become a successful target of cancer therapy. Microtubule-targeting agents, such as vinca alkaloids and taxanes, were used in clinic over 50 years. In past decades, development of new antimicrotubule agents that possess different structure and binding sites of tubulin has shown potent activity against the proliferation of various cancer cells, as well as in multidrug-resistant cancers. Interestingly, many of these agents represent an attractive ability that targeting the tumor blood vessels results in tumor vascular disruption. Therefore, exploring new agents and strategies may provide more effective therapeutic options in the related treatment of cancer. Areas covered: In past few years, there are many chemical compounds that successfully interferes the microtubules and display antitumor effect. In these, published compounds supply the fresh minds in modification of present drugs and new insights into the development of tubulin inhibitors. Expert opinion: This article arranges the microtubule-targeting agents that have published in patent in recent years. It may help in the investigation of new tubulin binding site and development of novel drug candidate in the future.
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A Novel Staphylococcal Cassette Chromosomal Element, SCCfusC, Carrying fusC and speG in Fusidic Acid-Resistant Methicillin-Resistant Staphylococcus aureus.
Antimicrob. Agents Chemother.
PUBLISHED: 11-25-2013
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The high prevalence of fusC (16/46, 59%) was found in fusidic acid-resistant methicillin-resistant Staphylococcus aureus isolates collected from 2008 to 2010. Nucleotide sequencing of fusC and flanking regions revealed a novel SCC structure, SCCfusC, which was integrated into rlmH and located upstream of SCCmec. The SCCfusC element contained speG, which may contribute to the polyamine resistance.
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Novel ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions in ossifying fibromyxoid tumors-molecular characterization shows genetic overlap with endometrial stromal sarcoma.
Genes Chromosomes Cancer
PUBLISHED: 10-15-2013
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PHF1 gene rearrangements have been recently described in around 50% of ossifying fibromyxoid tumors (OFMT) including benign and malignant cases, with a small subset showing EP400-PHF1 fusions. In the remaining cases no alternative gene fusions have been identified. PHF1-negative OFMT, especially if lacking S100 protein staining or peripheral ossification, are difficult to diagnose and distinguish from other soft tissue mimics. In seeking more comprehensive molecular characterization, we investigated a large cohort of 39 OFMT of various anatomic sites, immunoprofiles and grades of malignancy. Tumors were screened for PHF1 and EP400 rearrangements by FISH. RNA sequencing was performed in two index cases (OFMT1, OFMT3), negative for EP400-PHF1 fusions, followed by FusionSeq data analysis, a modular computational tool developed to discover gene fusions from paired-end RNA-seq data. Two novel fusions were identified ZC3H7B-BCOR in OFMT1 and MEAF6-PHF1 in OFMT3. After being validated by FISH and RT-PCR, these abnormalities were screened on the remaining cases. With these additional gene fusions, 33/39 (85%) of OFMTs demonstrated recurrent gene rearrangements, which can be used as molecular markers in challenging cases. The most common abnormality is PHF1 gene rearrangement (80%), being present in benign, atypical and malignant lesions, with fusion to EP400 in 44% of cases. ZC3H7B-BCOR and MEAF6-PHF1 fusions occurred predominantly in S100 protein-negative and malignant OFMT. As similar gene fusions were reported in endometrial stromal sarcomas, we screened for potential gene abnormalities in JAZF1 and EPC1 by FISH and found two additional cases with EPC1-PHF1 fusions. © 2013 Wiley Periodicals, Inc.
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Effect of glycemic control on microalbuminuria development among type 2 diabetes with high-normal albuminuria.
Ren Fail
PUBLISHED: 09-13-2013
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Abstract This study was aimed at revealing the factors and the interrelationships between factors on microalbuminuria development among type 2 diabetes (T2D) patients. Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to-creatinine ratio (UACR) of <30?mg/g, and an estimated glomerular filtration rate (eGFR) of >60?mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical analysis had revealed that the higher baseline UACR (10?mg/g; sensitivity, 80.9%, specificity, 63.6%; AUC?=?0.774) and glycohemoglobin level (HbA1c) (8%; sensitivity, 72.1%, specificity, 61.6%; AUC?=?0.698) were the two independent microalbuminuria risk factors. When considering the risk of microalbuminuria, the data were normalized with respect to subjects with low-normal UACR (<10?mg/g) and HbA1c??8%, high-normal UACR/HbA1c?8% were 2.59 (p?=?0.107), 6.15 (p?=?0.001), and 16.96 (p?10%) showed a progressively increase of the hazard risk in baseline high-normal UACR group. But the same correlation was not shown in the low-normal UACR group. This study identified the relationships of high-normal albuminuria and glycemic control on microalbuminuria development among T2D patients. Glycemic control is especially beneficial for T2D patients with baseline high-normal UACR in preventing microalbuminuria development.
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Protective effects of Zhibai Dihuang Wan on renal tubular cells affected with gentamicin-induced apoptosis.
J Ethnopharmacol
PUBLISHED: 09-06-2013
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Zhibai Dihuang Wan (ZDW) is an ancient traditional Chinese medicine composed of eight herbal ingredients and has been used to treat chronic kidney inflammation and diabetes for thousands of years. Nonetheless, the influence of ZDW on acute kidney injury is still unknown. We intended to identify the influence of ZDW on cell growth and gentamicin-induced apoptotic injury in renal tubular cells.
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Vertebral osteomyelitis caused by vancomycin-tolerant methicillin-resistant Staphylococcus aureus bacteremia: Experience with teicoplanin plus fosfomycin combination therapy.
J Microbiol Immunol Infect
PUBLISHED: 08-30-2013
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An 85-year-old female presented with fever and consciousness disturbance for 3 days. The patients blood culture subsequently revealed persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia despite the administration of vancomycin or teicoplanin monotherapy. Gallium inflammation scan and magnetic resonance image of the spine disclosed osteomyelitis and discitis at the level of L4-5. Surgical debridement was not feasible in this debilitated patient. Because of the creeping minimal inhibitory concentration of vancomycin of the causative isolate (1.5 ?g/mL) and clinical failure with glycopeptide monotherapy, we changed the antibiotic therapy to a fosfomycin and teicoplanin combination therapy. The patient showed improved clinical response in terms of her enhanced consciousness as well as subsidence of persisted bacteremia. Despite the potential side effects of fosfomycin (such as diarrhea and hypernatremia), it combined with a glycopeptide may be an alternative therapy for invasive refractory MRSA infections.
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New structure of phage-related islands carrying fusB and a virulence gene in fusidic acid-resistant Staphylococcus epidermidis.
Antimicrob. Agents Chemother.
PUBLISHED: 08-26-2013
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Nucleotide sequencing of the fusB-flanking regions in two fusidic acid-resistant Staphylococcus epidermidis isolates with the type IV aj1-leader peptide (LP)-fusB structure (lacking aj1) revealed that their fusB gene was located on novel phage-related islands inserted downstream of smpB and are here referred to as SeRIfusB-3692 and SePIfusB-857. The novel SePIfusB-857 structure was followed by SeCI857, forming a composite pathogenicity island which contained a putative virulence gene, vapE. The linkage of fusB and vapE may contribute to bacterial adaption.
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Imprinted genes and satellite loci are differentially methylated in bovine somatic cell nuclear transfer clones.
Cell Reprogram
PUBLISHED: 08-20-2013
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In mammals, genome-wide epigenetic reprogramming systems exist in primordial germ cells and zygotes. These reprogramming systems play crucial roles in regulating genome functions during critical stages of embryonic development, and they confer the stability of gene expression during mammalian development. The frequent unexpected loss of progeny from somatic cell nuclear transfer (SCNT) is an ongoing problem. In this study, we used six cloned bovines (named NT-1 to NT-6), which were created by ear fibroblast nuclear transfer and displayed short life spans with multiple organ defects, as an experimental model. We focus here on three imprinted genes (IGF2, H19, and XIST) and four satellite loci (Satellite I, Satellite II, Art2, and VNTR) to investigate their methylation changes. The results revealed that aberrant methylation frequently occurred in the analyzed imprinted genes, but not in the satellite loci, of the cloned bovines. After the bovine fibroblast cells were treated with the 5-aza-2()-deoxycytidine (5-Aza-dc) demethylation agent, the methylation percentages of the XIST and H19 putative differentially methylated region (DMR) were significantly decreased (XIST, p<0.01; H19, p<0.05) followed by an increase in their mRNA expression levels (p<0.01). Furthermore, we found that five short-lived cloned bovines (NT-1 to NT-5) exhibited more severe aberrant methylation changes in the three imprinted genes examined than the little longer-lived clone (NT-6) compared with wild-type (WT) cows. Our data suggest that the reprogramming of the methylation-controlled regions between the imprinted genes and satellite loci are differences and may be involved with additional mechanisms that need further elucidation.
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Three-Dimensional Molybdenum Sulfide Sponges for Electrocatalytic Water Splitting.
Small
PUBLISHED: 08-06-2013
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Electroactive MoSx catalysts on porous 3D sponges synthezied by a simple and scalable thermolysis process are proposed. Although no conducting materials are used to host the MoSx catalysts, they still serve as efficient electrodes for hydrogen evolution. The high current density of the MoSx-coated sponges are attributed to the large electrochemical surface area and their S-rich chemical structure.
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The LIM domain only 4 protein is a metabolic responsive inhibitor of protein tyrosine phosphatase 1B that controls hypothalamic leptin signaling.
J. Neurosci.
PUBLISHED: 08-02-2013
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Protein tyrosine phosphatase 1B (PTP1B) counteracts leptin signaling and is a therapeutic target for obesity and diabetes. Here we found that LIM domain only 4 (LMO4) inhibits PTP1B activity by increasing the oxidized inactive form of PTP1B. Mice with neuronal ablation of LMO4 have elevated PTP1B activity and impaired hypothalamic leptin signaling, and a PTP1B inhibitor normalized PTP1B activity and restored leptin control of circulating insulin levels. LMO4 is palmitoylated at its C-terminal cysteine, and deletion of this residue prevented palmitoylation and retention of LMO4 at the endoplasmic reticulum and abolished its inhibitory effect on PTP1B. Importantly, LMO4 palmitoylation is sensitive to metabolic stress; mice challenged with a brief high-fat diet or acute intracerebroventricular infusion of saturated fatty acid had less palmitoylated LMO4, less oxidized PTP1B, and increased PTP1B activity in the hypothalamus. Thus, unleashed PTP1B activity attributable to loss of LMO4 palmitoylation may account for rapid loss of central leptin signaling after acute exposure to saturated fat.
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VH1-44 gene usage defines a subset of canine B-cell lymphomas associated with better patient survival.
Vet. Immunol. Immunopathol.
PUBLISHED: 07-27-2013
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The use of specific immunoglobulin heavy chain variable region (VH) genes has been associated with increased patient survival in human B-cell lymphomas (hBCL). Given the similarity of human and canine BCL (cBCL) in morphology and clinical treatment, we examined the choice of VH in cBCL and determined whether VH gene selection was a distinct feature associated with survival time in dogs. VH gene selection and mutational status in 52 cBCL, including 29 diffuse large B-cell lymphomas (cDLBCL, the most common subtype of cBCL), were analyzed by comparison with the 80 published canine germline VH gene sequences. We further examined the prognostic impact of the subgroups defined by these features on canine survival. We found that VH1-44 was preferentially expressed in the majority of the 52 cBCLs (60%) as well as in the majority of the cDLBCL subset (59%). VH1-44 gene expression was associated with a statistically better overall survival (p=0.039) in cBCL patients, as well as in the cDLBCL subset of patients (p=0.038). These findings suggest that VH gene selection in cBCL is not random and may therefore have functional implications for cBCL lymphomagenesis, in addition to being a useful prognostic biomarker.
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Successful treatment of drug-induced acute liver failure with high-volume plasma exchange.
J Clin Apher
PUBLISHED: 07-02-2013
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We report two patients with drug-induced liver injury (DILI)-related acute liver failure (ALF) who were successfully treated with high-volume plasma exchange without liver transplantation. The first patient was a 66-year-old man admitted because of a perforated duodenal ulcer complicated with peritonitis and septic shock. After treatment with multiple antibiotics, the patient developed DILI and ALF. Grade 3 hepatic encephalopathy and profound jaundice were present. Symptoms and signs of ALF improved dramatically after initiation of plasma exchange. The patient was discharged uneventfully. The second patient was a 94-year-old man admitted for treatment of newly diagnosed pulmonary tuberculosis. DILI and ALF developed 5 days after initiation of anti-tuberculosis treatment. Grade 4 hepatic encephalopathy was present. After plasma exchange, the patients level of consciousness improved dramatically, and he recovered from ALF. These 2 cases show the potential of plasma exchange in the treatment of DILI despite occurrence acute liver failure. J. Clin. Apheresis, 2013. © 2013 Wiley Periodicals, Inc.
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Novel MIR143-NOTCH fusions in benign and malignant glomus tumors.
Genes Chromosomes Cancer
PUBLISHED: 06-19-2013
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Glomus tumors (GT) have been classified among tumors of perivascular smooth muscle differentiation, together with myopericytoma, myofibroma/tosis, and angioleiomyoma, based on their morphologic overlap. However, no molecular studies have been carried out to date to investigate their genetic phenotype and to confirm their shared pathogenesis. RNA sequencing was performed in three index cases (GT1, malignant GT; GT2, benign GT and M1, multifocal myopericytoma), followed by FusionSeq data analysis, a modular computational tool developed to discover gene fusions from paired-end RNA-seq data. A gene fusion involving MIR143 in band 5q32 was identified in both GTs with either NOTCH2 in 1p13 in GT1 or NOTCH1 in 9q34 in GT2, but none in M1. After being validated by FISH and RT-PCR, these abnormalities were screened on 33 GTs, 6 myopericytomas, 9 myofibroma/toses, 18 angioleiomyomas and in a control group of 5 sino-nasal hemangiopericytomas. Overall NOTCH2 gene rearrangements were identified in 52% of GT, including all malignant cases and one NF1-related GT. No additional cases showed NOTCH1 rearrangement. As NOTCH3 shares similar functions with NOTCH2 in regulating vascular smooth muscle development, the study group was also investigated for abnormalities in this gene by FISH. Indeed, NOTCH3 rearrangements were identified in 9% of GTs, all present in benign soft tissue GT, one case being fused to MIR143. Only 1/18 angioleiomyomas showed NOTCH2 gene rearrangement, while all the myopericytomas and myofibroma/toses were negative. In summary, we describe novel NOTCH1-3 rearrangements in benign and malignant, visceral, and soft tissue GTs.
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Gene profiling of canine B-cell lymphoma reveals germinal center and postgerminal center subtypes with different survival times, modeling human DLBCL.
Cancer Res.
PUBLISHED: 06-19-2013
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Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, and fewer than half of patients are cured with standard first-line therapy. To improve therapeutic options, better animal models that accurately mimic human DLBCL (hDLBCL) are needed. Canine DLBCL, one of the most common cancers in veterinary oncology, is morphologically similar to hDLBCL and is treated using similar chemotherapeutic protocols. With genomic technologies, it is now possible to molecularly evaluate dogs as a potential large-animal model for hDLBCL. We evaluated canine B-cell lymphomas (cBCL) using immunohistochemistry (IHC) and gene expression profiling. cBCL expression profiles were similar in many ways to hDLBCLs. For instance, a subset had increased expression of NF-?B pathway genes, mirroring human activated B-cell (ABC)-type DLBCL. Furthermore, immunoglobulin heavy chain ongoing mutation status, which is correlated with ABC/germinal center B-cell cell of origin in hDLBCL, separated cBCL into two groups with statistically different progression-free and overall survival times. In contrast with hDLBCL, cBCL rarely expressed BCL6 and MUM1/IRF4 by IHC. Collectively, these studies identify molecular similarities to hDLBCL that introduce pet dogs as a representative model of hDLBCL for future studies, including therapeutic clinical trials.
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Therapeutic Potential of Andrographolide Isolated from the Leaves of Andrographis paniculata Nees for Treating Lung Adenocarcinomas.
Evid Based Complement Alternat Med
PUBLISHED: 06-05-2013
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Andrographolide is one of the major diterpene lactones found in Andrographis paniculata Nees and exhibits remarkable inhibitory effects on various cancers. In this study, the antipulmonary cancer effects of andrographolide were studied in a lung tumor mouse model induced by human vascular endothelial growth factor A 165 (hVEGF-A165). These results demonstrated that andrographolide significantly reduced the expression of hVEGF-A165 compared with a mock group in the Clara cells of the lungs. In addition, andrographolide also decreased tumor formation by reducing VEGF, EGFR, Cyclin A, and Cyclin B expression on the transcriptional and translational levels. These results indicated that andrographolide treatment on the overexpression of VEGF can arrest the cell cycle, which induced pulmonary tumors in transgenic mice. In conclusion, the antiangiogenesis and chemotherapeutic potential of andrographolide may provide a cure for pulmonary tumors in the future.
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Fructo-oligosaccharide attenuates the production of pro-inflammatory cytokines and the activation of JNK/Jun pathway in the lungs of D-galactose-treated Balb/cJ mice.
Eur J Nutr
PUBLISHED: 06-04-2013
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PURPOSE: This study determined the effects of long-term D-galactose (DG) injection on the lung pro-inflammatory and fibrotic status and whether fructo-oligosaccharide (FO) could attenuate such effects. METHODS: Forty Balb/cJ mice (12 weeks of age) were divided into four groups: control (s.c. saline) (basal diet), DG (s.c. 1.2 g DG/kg body weight) (basal diet), DG + FO (FO diet, 2.5 % w/w FO), and DG + E (vitamin E diet, ?-tocopherol 0.2 % w/w) serving as an antioxidant control group. These animals were killed after 49 day of treatments. Another group of naturally aging (NA) mice without any injection was killed at 64 weeks of age to be an aging control group. RESULTS: D-galactose treatment, generally similar to NA, increased the lung pro-inflammatory status, as shown in the IL-6 and IL-1? levels and the expression of phospho-Jun and phospho-JNK, and the fibrotic status as shown in the hydroxyproline level compared to the vehicle. FO diminished the DG-induced increases in the lung IL-1? level and expressions of total Jun, phospho-JNK, and attenuated DG effects on lung IL-6 and hydroxyproline, while ?-tocopherol exerted anti-inflammatory effects on all parameters determined. FO, as well as ?-tocopherol, modulated the large bowel ecology by increasing the fecal bifidobacteria and cecal butyrate levels compared with DG. CONCLUSIONS: D-galactose treatment mimicked the lung pro-inflammatory status as shown in the NA mice. FO attenuated the DG-induced lung pro-inflammatory status and down-regulated JNK/Jun pathway in the lung, which could be mediated by the prebiotic effects and metabolic products of FO in the large intestine.
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High-frequency ultrasound imaging to evaluate liver fibrosis progression in rats and yi guan jian herbal therapeutic effects.
Evid Based Complement Alternat Med
PUBLISHED: 06-01-2013
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The animals used in liver fibrosis studies must usually be sacrificed. Ultrasound has been demonstrated to have the ability to diagnose hepatic fibrosis and cirrhosis in experimental small-animal models. However, few studies have used high-frequency ultrasound (HFU, 40?MHz) to monitor changes in the rat liver and other hollow organs longitudinally. In this study, liver fibrosis was induced by administering dimethylnitrosamine (DMN) in SD rats, aged 8 weeks, for three consecutive days per week for up to 4 weeks. A Chinese herbal medicine Yi Guan Jian (YGJ) was orally administered (1.8?g/kg daily) to DMN-induced liver fibrosis rats for 2 weeks. Compared with the normal control rats, rats treated with DMN for either 2 weeks or 4 weeks had significantly lower body weights, liver indexes and elevation of hydroxyproline, GOT, and GPT contents. YGJ herbal treatment remarkably prevented rats from DMN-induced liver fibrosis. The HFU scoring results among the normal controls, 2-week DMN-treated rats, 4-week DMN-treated rats, and combined 2-week YGJ therapy with 4-week DMN-treated rats also reached statistical significance. Thus, HFU is an accurate tool for the longitudinal analysis of liver fibrosis progression in small-animal models, and the YGJ may be useful in reversing the development of hepatic fibrosis.
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Molecular adsorption induces the transformation of rhombohedral- to Bernal-stacking order in trilayer graphene.
Nat Commun
PUBLISHED: 05-30-2013
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The Bernal (ABA)-stacked graphene trilayer is presumed to be thermodynamically more stable than the rhombohedral (ABC) counterpart. However, the thermal transformation from ABC to ABA domains does not occur at a temperature lower than 1,000?°C. Here we report that ABC-stacked trilayers are transformed to ABA-stacked layers after an organic molecule triazine is evaporated onto graphene surfaces at 150?°C. The transformation is found to always initiate at the ABA-ABC domain boundaries. Simulations based on density function theory considering the van der Waals interaction suggest that after triazine decoration the energy difference between ABA and ABC domains is larger, providing a driving force for stacking transformation. The molecular dynamics simulation results further suggest that the triazine decoration on the wrinkles at the ABC-ABA domain boundary activates the wrinkle sliding toward the ABC domains, leading to the stacking transformation from ABC to ABA.
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Renin-angiotensin system blockade in heart failure patients on long-term haemodialysis in Taiwan.
Eur. J. Heart Fail.
PUBLISHED: 05-12-2013
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Heart failure is among the most frequent complications of patients on long-term haemodialysis. The benefits of renin-angiotensin system (RAS) blockade on the outcomes of these patients have yet to be determined.
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Molecular Mechanisms of Treadmill Therapy on Neuromuscular Atrophy Induced via Botulinum Toxin A.
Neural Plast.
PUBLISHED: 05-09-2013
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Botulinum toxin A (BoNT-A) is a bacterial zinc-dependent endopeptidase that acts specifically on neuromuscular junctions. BoNT-A blocks the release of acetylcholine, thereby decreasing the ability of a spastic muscle to generate forceful contraction, which results in a temporal local weakness and the atrophy of targeted muscles. BoNT-A-induced temporal muscle weakness has been used to manage skeletal muscle spasticity, such as poststroke spasticity, cerebral palsy, and cervical dystonia. However, the combined effect of treadmill exercise and BoNT-A treatment is not well understood. We previously demonstrated that for rats, following BoNT-A injection in the gastrocnemius muscle, treadmill running improved the recovery of the sciatic functional index (SFI), muscle contraction strength, and compound muscle action potential (CMAP) amplitude and area. Treadmill training had no influence on gastrocnemius mass that received BoNT-A injection, but it improved the maximal contraction force of the gastrocnemius, and upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and acetylcholine receptor (AChR) subunits ? and ? was found following treadmill training. Taken together, these results suggest that the upregulation of genes associated with neurite and AChR regeneration following treadmill training may contribute to enhanced gastrocnemius strength recovery following BoNT-A injection.
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Using induced electroosmotic micromixer to enhance the reproducibility of chemiluminescence intensity.
Electrophoresis
PUBLISHED: 04-19-2013
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In this study, induced electroosmotic vortex flows were generated using an AC electric field by one pair of external electrodes to rapidly mix luminescence reagents in a 30 ?L micromixer and enhance the reproducibility of chemiluminescence (CL) assays. A solution containing the catalyst reagent ferricyanide ions (4 ?L) was pipetted into a reservoir containing luminol to produce CL in the presence of hydrogen peroxide. When the added ferricyanide aliquot contacted the reservoir solution, the CL began flashing, but rapidly diminished as the ferricyanide was consumed. In such a short illumination period, the solutes could not mix homogeneously. Therefore, the reproducibility of CL intensities collected using a CCD and multiple aliquot additions was determined to be inadequate. By contrast, when the solutes were efficiently mixed after adding a ferricyanide aliquot to a micromixer, the intensity reproducibility was significantly improved. When the CL temporal profile was analyzed using a PMT, a consistent improvement in reproducibility was observed between the CL intensity and estimated CL reaction rate. Replicating the proposed device would create a multiple well plate that contains a micromixer in each reservoir; this system is compatible with conventional CL instrumentation and requires no CL enhancer to slow a reaction.
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Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma.
Genes Chromosomes Cancer
PUBLISHED: 04-15-2013
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Conventional epithelioid hemangioendotheliomas (EHE) have a distinctive morphologic appearance and are characterized by a recurrent t(1;3) translocation, resulting in a WWTR1-CAMTA1 fusion gene. We have recently encountered a fusion-negative subset characterized by a somewhat different morphology, including focally well-formed vasoformative features, which was further investigated for recurrent genetic abnormalities. Based on a case showing strong transcription factor E3 (TFE3) immunoreactivity, fluorescence in situ hybridization (FISH) analysis for TFE3 gene rearrangement was applied to the index case as well as to nine additional cases, selected through negative WWTR1-CAMTA1 screening. A control group, including 18 epithelioid hemangiomas, nine pseudomyogenic HE, and three epithelioid angiosarcomas, was also tested. TFE3 gene rearrangement was identified in 10 patients, with equal gender distribution and a mean age of 30 years old. The lesions were located in somatic soft tissue in six cases, lung in three and one in bone. One case with available frozen tissue was tested by RNA sequencing and FusionSeq data analysis to detect novel fusions. A YAP1-TFE3 fusion was thus detected, which was further validated by FISH and reverse transcription polymerase chain reaction (RT-PCR). YAP1 gene rearrangements were then confirmed in seven of the remaining nine TFE3-rearranged EHEs by FISH. No TFE3 structural abnormalities were detected in any of the controls. The TFE3-rearranged EHEs showed similar morphologic features with at least focally, well-formed vascular channels, in addition to a variably solid architecture. All tumors expressed endothelial markers, as well as strong nuclear TFE3. In summary, we are reporting a novel subset of EHE occurring in young adults, showing a distinct phenotype and YAP1-TFE3 fusions.
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Ingestion of milk containing the Dp2 peptide, a dust mite allergen, protects mice from allergic airway inflammation and hyper-responsiveness.
Allergy Asthma Clin Immunol
PUBLISHED: 04-14-2013
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Allergen-specific immunotherapy has been demonstrated to have potential for the treatment of allergic diseases. Transgenic animals are currently the best available bioreactors to produce recombinant proteins, which can be secreted in milk. It has not been clearly demonstrated whether milk from transgenic animals expressing recombinant allergens has immunomodulatory effects on allergic asthma.
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Urotensin II exerts antiapoptotic effect on NRK-52E cells through prostacyclin-mediated peroxisome proliferator-activated receptor alpha and Akt activation.
Mol. Cell. Endocrinol.
PUBLISHED: 03-25-2013
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Urotensin II (UII) is a cyclic vasoactive peptide which is mainly expressed in kidneys. Although elevated plasma UII levels are associated with renal impairment, the influence of UII on renal injury is unclear. In this study, we monitored the influence of UII on gentamicin-induced apoptosis in rat tubular cells (NRK-52E). We found that UII significantly reduced gentamicin-induced apoptosis and apoptotic signals. Blocking endogenous UII secretion caused cells to be more susceptible to gentamicin. In gentamicin-treated mice, UII also expressed protective effect on renal tubular cells. UII was also found to induce prostacyclin (PGI2) production, which caused peroxisomal proliferator-activated receptor ? (PPAR?) activation as revealed by both PGI2 synthase siRNA transfection and piroxicam treatment. Blockage of PPAR? by siRNA transfection inhibited UII-induced Akt phosphorylation and the antiapoptotic effect of UII. Our results suggest that UII can protect renal tubular cells from gentamicin-induced apoptosis through PGI2-mediated PPAR? and Akt activation.
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High-gain phototransistors based on a CVD MoS? monolayer.
Adv. Mater. Weinheim
PUBLISHED: 03-19-2013
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A phototransistor based on a chemical vapor deposited (CVD) MoS2 monolayer exhibits a high photoresponsivity (2200 A W(-1) ) and an excellent photogain (5000). The presence of shallow traps contributes to the persistent photoconductivity. Ambient adsorbates act as p-dopants to MoS2 , decreasing the carrier mobility, photoresponsivity, and photogain.
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Ring chromosome 21 presenting with sacrococcygeal teratoma: prenatal diagnosis, molecular cytogenetic characterization and literature review.
Gene
PUBLISHED: 03-13-2013
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We present perinatal findings and molecular cytogenetic characterization of a prenatally detected sacrococcygeal teratoma associated with mosaic r(21). This is the first report of mosaic r(21) presenting with a fetal sacrococcygeal teratoma. We discuss cytogenetic abnormalities associated with fetal sacrococcygeal teratomas.
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