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Find video protocols related to scientific articles indexed in Pubmed.
Emulated laser-acupuncture system.
Appl Opt
PUBLISHED: 10-17-2014
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A novel laser-acupuncture system was developed that can be used to implement the manipulation methods of traditional acupuncture, such as lifting and thrusting. A 780 nm laser diode with a maximum power of 90 mW was used as the light source. The focus point of the laser beam was adjustable by changing the position of the lens, facilitating the implementation of the lifting and thrusting methods of traditional Chinese medicine and achieving various stimulation depths at the acupuncture point. The images for the light spots from the outlet of the emulated laser acupuncture were captured at various distances and their sizes were calculated. The result showed that the diameter of the focused light spot (i.e., at the focus point) was 0.11 mm, which is close to the diameter of commonly used needles (with diameters of approximately 0.22 mm). The area of the light spot 1 cm from the focus point was approximately 50 times larger, indicating that the unit power might be 1/50 of the power of the focus point. To study the effect of emulated laser acupuncture on human meridians, after stimulating the Shenmen point (HT7) of five subjects and obtaining their Ryodoraku values of the heart meridian and the small-intestine meridian, a paired t test showed that the laser stimulation incorporating lifting and thrusting was significantly higher than the laser stimulation without lifting and thrusting (p<0.05). The result is consistent with traditional acupuncture in that acupuncture incorporating lift and thrust is more effective than that without lift and thrust.
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The application of flow cytometry for evaluating biological aggressiveness of intracranial meningiomas.
Cytometry B Clin Cytom
PUBLISHED: 09-23-2014
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Meningiomas have classically been considered to include benign and atypical/anaplastic tumors. Despite the availability of clinical and pathologic parameters for prognostic prediction prognosis, the behavior of each meningioma may be difficult to predict. Here, we used DNA flow-cytometric studies to predict biological tumor behaviors of intracranial meningiomas.
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Metal-Free ?-Bond Metathesis in 1,3,2-Diazaphospholene-Catalyzed Hydroboration of Carbonyl Compounds.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 09-02-2014
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The first metal-free catalytic hydroboration of carbonyl derivatives has been developed in which a catalytic amount of 1,3,2-diazaphospholene effectively promotes a hydroboration reaction of aliphatic and aromatic aldehydes and ketones. The reaction mechanism involves the cleavage of both the P?O bond of the alkoxyphosphine intermediate and the B?H bond of pinacolborane as well as the formation of P?H and B?O bonds. Thus, the reaction proceeds through a non-metal ?-bond metathesis. Kinetic and computational studies suggest that the ?-bond metathesis occurred in a stepwise but nearly concerted manner.
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A retrospective review of the prognostic value of ALDH-1, Bmi-1 and Nanog stem cell markers in esophageal squamous cell carcinoma.
PLoS ONE
PUBLISHED: 08-22-2014
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Stem cell markers are upregulated in various cancers and have potential as prognostic indicators. The objective of this study was to determine the expression of three stem cell markers, aldehyde dehydrogenase 1 (ALDH-1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), and Nanog, in esophageal squamous cell carcinoma (ESCC) tissues. Immunohistochemistry was used to measure the expression of ALDH-1, Bmi-1, and Nanog in ESCC tissues from 41 patients who received pre-operative chemoradiation. We evaluated the relationship between expression of these markers, and clinicopathological features, tumor regression grade (TRG), and 5-year overall survival (OS). There were no significant associations of ALDH-1 or Bmi-1 expression with age, gender, clinical stage, and treatments (p>0.05). However, patients with Nanog-positive tumors were significantly older than those whose tumors were Nanog-negative (p?=?0.033). TRG after treatment was significantly associated with expression of ALDH-1 (p?=?0.001), Bmi-1 (p?=?0.004), and Nanog (p<0.001). Although OS was significantly better in patients with low TRGs (p?=?0.001), there were no significant correlations between ALDH-1, Bmi-1, or Nanog with OS. Expression of ALDH-1, Bmi-1, and Nanog correlated with TRG, but not OS. Further large studies are necessary to fully elucidate the prognostic value of these stem cell markers for ESCC patients.
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SDF-1? stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II.
Int. J. Cancer
PUBLISHED: 08-18-2014
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Multiple myeloma (MM) is a B lymphocyte malignancy that remains incurable despite extensive research efforts. This is due, in part, to frequent disease recurrences associated with the persistence of myeloma cancer stem cells (mCSCs). Bone marrow mesenchymal stromal cells (BMSCs) play critical roles in supporting mCSCs through genetic or biochemical alterations. Previously, we identified mechanical distinctions between BMSCs isolated from MM patients (mBMSCs) and those present in the BM of healthy individuals (nBMSCs). These properties of mBMSC contributed to their ability to preferentially support mCSCs. To further illustrate mechanisms underlying the differences between mBMSCs and nBMSCs, here we report that (i) mBMSCs express an abnormal, constitutively high level of phosphorylated Myosin II, which leads to stiffer membrane mechanics, (ii) mBMSCs are more sensitive to SDF-1?-induced activation of MYL2 through the G(i./o) -PI3K-RhoA-ROCK-Myosin II signaling pathway, affecting Young's modulus in BMSCs and (iii) activated Myosin II confers increased cell contractile potential, leading to enhanced collagen matrix remodeling and promoting the cell-cell interaction between mCSCs and mBMSCs. Together, our findings suggest that interfering with SDF-1? signaling may serve as a new therapeutic approach for eliminating mCSCs by disrupting their interaction with mBMSCs.
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De novo CD3 negative hepatosplenic T-cell lymphoma: diagnostic challenges and pitfalls.
Arch. Pathol. Lab. Med.
PUBLISHED: 07-01-2014
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Hepatosplenic T-cell lymphoma is a rare and aggressive peripheral T-cell malignancy that is distinctively characterized by sinusoidal infiltration of mature medium-sized T lymphocytes in the spleen and liver. The neoplastic cells are classically surface CD3(+), CD2(+), CD5(-), CD4(-), and CD8(+/-) and manifest variable expression of markers associated with natural killer (NK) cells such as CD16 and CD56. In this article, we report the first case to date of a newly diagnosed de novo surface CD3(-) hepatosplenic T-cell lymphoma with circulating blastlike neoplastic cells expressing NK-cell-associated markers. The lack of surface CD3 expression, together with the expression of NK-cell-associated markers and the leukemic presentation, leads to significant diagnostic challenges in differentiating this CD3(-) hepatosplenic T-cell lymphoma from NK-cell neoplasms, in particular aggressive NK-cell leukemia. The related literature is reviewed, and the approaches for adequate diagnosis of this novel situation are described.
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High-grade glioma in a patient with breast cancer.
Asian J Surg
PUBLISHED: 06-28-2014
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Breast cancer is one of the most common origins of metastatic lesions in the central nervous system. Many patients with a breast cancer and concurrent brain tumor(s) were diagnosed to have a metastatic lesion or lesions in the brain, based exclusively on their image findings without further pathologic verification, and received radiotherapy alone thereafter. It is, however, possible that a different pathology such as primary brain malignancy, which actually warrants a specific treatment modality, may occur in such patients with an already known malignancy. We, herein, reported a 61-year-old female patient who suffered from an anaplastic oligodendroglioma 1 year after her diagnosis of breast cancer. Demographic data, characteristic imaging findings, treatment, and outcome of the patient were discussed.
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1,2,4,3-Triazaborole-based neutral oxoborane stabilized by a Lewis acid.
Chem. Commun. (Camb.)
PUBLISHED: 06-24-2014
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The first example of 1,2,4,3-triazaborole-based oxoborane has been synthesized via hydrogen migration upon the coordination of AlCl3 to the corresponding borinic acid. X-ray diffraction analysis and computational study disclosed the partial B[double bond, length as m-dash]O double-bond property.
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Sulforaphane down-regulates SKP2 to stabilize p27(KIP1) for inducing antiproliferation in human colon adenocarcinoma cells.
J. Biosci. Bioeng.
PUBLISHED: 06-02-2014
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Sulforaphane is a cruciferous vegetable-derived isothiocyanate with promising chemopreventive and therapeutic activities. Induction of proliferation arrest and apoptosis principally contribute to sulforaphane's anticancer activity, but the precise molecular mechanisms remain elusive. The oncoprotein SKP2 is a key component of the SKP1-CULLIN1-F-box (SCF) E3 ligase complex and is responsible for directing SCF-mediated degradation of cyclin-dependent kinase inhibitor p27(KIP1) to promote cell proliferation. We herein provide the first evidence supporting the critical involvement of the SKP2-p27(KIP1) axis in sulforaphane-induced antiproliferation in various human colon adenocarcinoma cell lines. Specifically, sulforaphane markedly suppressed the levels of BrdU incorporation and clonogenicity in all tested cell lines, illustrating the antiproliferative effect of sulforaphane. Of note, sulforaphane-induced antiproliferation was accompanied with down-regulation of SKP2, leading to the stabilization and thus up-regulation of p27(KIP1). Additionally, sulforaphane was found to down-regulate SKP2 mainly through transcriptional repression, as sulforaphane lowered SKP2 mRNA expression and the SKP2 promoter activity. Furthermore, sulforaphane treatment led to the activation of both AKT and ERK, thus ruling out the possibility that sulforaphane down-regulates SKP2 by inhibiting AKT or ERK. Notably, sulforaphane-elicited suppression of BrdU incorporation and clonogenicity were significantly rescued in the context of SKP2 overexpression or p27(KIP1) depletion, therefore highlighting the important role of SKP2 down-regulation and the ensuing stabilization of p27(KIP1) in sulforaphane-induced antiproliferation. Collectively, these data expand our molecular understanding about how sulforaphane elicits proliferation arrest, but also implicate the application of sulforaphane in therapeutic modalities targeting SKP2.
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Electrically and optically readable light emitting memories.
Sci Rep
PUBLISHED: 05-13-2014
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Electrochemical metallization memories based on redox-induced resistance switching have been considered as the next-generation electronic storage devices. However, the electronic signals suffer from the interconnect delay and the limited reading speed, which are the major obstacles for memory performance. To solve this problem, here we demonstrate the first attempt of light-emitting memory (LEM) that uses SiO2 as the resistive switching material in tandem with graphene-insulator-semiconductor (GIS) light-emitting diode (LED). By utilizing the excellent properties of graphene, such as high conductivity, high robustness and high transparency, our proposed LEM enables data communication via electronic and optical signals simultaneously. Both the bistable light-emission state and the resistance switching properties can be attributed to the conducting filament mechanism. Moreover, on the analysis of current-voltage characteristics, we further confirm that the electroluminescence signal originates from the carrier tunneling, which is quite different from the standard p-n junction model. We stress here that the newly developed LEM device possesses a simple structure with mature fabrication processes, which integrates advantages of all composed materials and can be extended to many other material systems. It should be able to attract academic interest as well as stimulate industrial application.
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Anti-cancer effects of ursane triterpenoid as a single agent and in combination with cisplatin in bladder cancer.
Eur. J. Pharmacol.
PUBLISHED: 05-01-2014
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Ursolic acid and most of its derivatives are cytotoxic to bladder cancer cells. An ursolic acid derivative, isopropyl 3?-hydroxyurs-12-en-28-oat (UA17), previously reported that it exhibited potent cytotoxicity against bladder cancer cells, NTUB1 cells. In this study, we further investigated the underlying mechanism of UA17 and evaluated its potential clinical use. UA17 may exert the onset of a p53-mediated p38 MAPK activation to up-regulate GADD153. GADD153, in turn, down-regulated Bcl-2 protein to cause mitochondrial membrane potential loss and apoptosis through intracellular ROS generation. In addition, UA17 markedly decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (CDK2 and CDK4), and caused increase of p21 and p27 levels. To assess the suitability of UA17 as a chemotherapeutic agent against NTUB1 cells, its cytotoxic effects have been further evaluated in the combination with cisplatin. The addition of UA17 to cisplatin induces possibly additive cell growth inhibition which correlated to the accumulation of S phase cells and a corresponding decrease in accumulation of G1 phase cells, accompanied an increased accumulation of sub-G1 phase cells. Furthermore, UA17/cisplatin combination exhibited increase of p21, cyclin E, and p-p53 level, and decrease of p27 and cyclin D1 proteins, and slightly diminishing the level of CDK2. P-p38 up-regulation induced by UA17/cisplatin combination through generation of ROS and Bcl-2 down-regulation induced by UA17/cisplatin combination increased cell death. Finally, the antitumorigenic effects of UA17 or UA17/cisplatin combination were further supported by their inhibition on growth of bladder tumor cells in a therapeutic murine MBT-2 bladder tumor model.
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Deletion of the gene encoding the reductase component of 3-ketosteroid 9¿-hydroxylase in.
Microb. Cell Fact.
PUBLISHED: 04-25-2014
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The gene encoding the putative reductase component (KshB) of 3-ketosteroid 9¿-hydroxylase was cloned from Rhodococcus equi USA-18, a cholesterol oxidase-producing strain formerly named Arthrobacter simplex USA-18, by PCR according to consensus amino acid motifs of several bacterial KshB subunits. Deletion of the gene in R. equi USA-18 by a PCR-targeted gene disruption method resulted in a mutant strain that could accumulate up to 0.58 mg/ml 1,4-androstadiene-3,17-dione (ADD) in the culture medium when 0.2% cholesterol was used as the carbon source, indicating the involvement of the deleted enzyme in 9¿-hydroxylation of steroids. In addition, this mutant also accumulated 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (¿1,4-BNC). Because both ADD and ¿1,4-BNC are important intermediates for the synthesis of steroid drugs, this mutant derived from R. equi USA-18 may deserve further investigation for its application potential.
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High throughput quantitative reverse transcription PCR assays revealing over-expression of cancer testis antigen genes in multiple myeloma stem cell-like side population cells.
Br. J. Haematol.
PUBLISHED: 04-09-2014
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Multiple myeloma (MM) stem cells, proposed to be responsible for the tumourigenesis, drug resistance and recurrence of this disease, are enriched in the cancer stem cell-like side population (SP). Cancer testis antigens (CTA) are attractive targets for immunotherapy because they are widely expressed in cancers but only in limited types of normal tissues. We designed a high throughput assay, which allowed simultaneous relative quantifying expression of 90 CTA genes associated with MM. In the three MM cell lines tested, six CTA genes were over-expressed in two and LUZP4 and ODF1 were universally up-regulated in all three cell lines. Subsequent study of primary bone marrow (BM) from eight MM patients and four healthy donors revealed that 19 CTA genes were up-regulated in SP of MM compared with mature plasma cells. In contrast, only two CTA genes showed a moderate increase in SP cells of healthy BM. Furthermore, knockdown using small interfering RNA (siRNA) revealed that LUZP4 expression is required for colony-forming ability and drug resistance in MM cells. Our findings indicate that multiple CTA have unique expression profiles in MM SP, suggesting that CTA may serve as targets for immunotherapy that it specific for MM stem cells and which may lead to the long-term cure of MM.
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Aldose reductase inhibition prevents endotoxin-induced inflammatory responses in retinal microglia.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 03-29-2014
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Retinal microglia become activated in diabetes and produce pro-inflammatory molecules associated with changes in retinal vasculature and increased apoptosis of retinal neurons and glial cells. We sought to determine if the action of aldose reductase (AR), an enzyme linked to the pathogenesis of diabetic retinopathy, contributes to activation of microglial cells.
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Self-polarized spin-nanolasers.
Nat Nanotechnol
PUBLISHED: 02-24-2014
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Besides adding a new functionality to conventional lasers, spin-polarized lasers can, potentially, offer lower threshold currents and reach higher emission intensities. However, to achieve spin-polarized lasing emission a material should possess a slow spin relaxation and a high propensity to be injected with spin-polarized currents. These are stringent requirements that, so far, have limited the choice of candidate materials for spin-lasers. Here we show that these requirements can be relaxed by using a new self-polarized spin mechanism. Fe3O4 nanoparticles are coupled to GaN nanorods to form an energy-band structure that induces the selective charge transfer of electrons with opposite spins. In turn, this selection mechanism generates the population imbalance between spin-up and spin-down electrons in the emitter's energy levels without an external bias. Using this principle, we demonstrate laser emission from GaN nanorods with spin polarization up to 28.2% at room temperature under a low magnetic field of 0.35 T. As the spin-selection mechanism relies entirely on the relative energy-band alignment between the iron oxide nanoparticles and the emitter and requires neither optical pumping with circularly polarized light nor electrical pumping with magnetic electrodes, potentially a wide range of semiconductors can be used as spin-nanolasers.
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Long-term cannabinoid type 2 receptor agonist therapy decreases bacterial translocation in rats with cirrhosis and ascites.
J. Hepatol.
PUBLISHED: 02-15-2014
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Intestinal hyperpermeability, impaired peritoneal macrophages (PMs) phagocytosis, and bacterial translocation (BT), resulting in increased systemic and local infection/inflammation such as spontaneous bacterial peritonitis (SBP) together with increased tumor necrosis factor-? (TNF?) levels, are all implicated in the pathogenesis of cirrhosis-related complications. Manipulation of the cannabinoid receptors (CB1R and CB2R), which are expressed on the gut mucosa and PMs, has been reported to modulate intestinal inflammation and systemic inflammatory cytokine release. Our study aims to explore the effects of chronic CB1R/CB2R agonist/antagonist treatments on relevant abnormalities in cirrhotic ascitic rats.
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Taurine protects HK-2 cells from oxidized LDL-induced cytotoxicity via the ROS-mediated mitochondrial and p53-related apoptotic pathways.
Toxicol. Appl. Pharmacol.
PUBLISHED: 02-14-2014
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Oxidized LDL (oxLDL) induces a pro-oxidative environment and promotes apoptosis, causing the progression of renal diseases in humans. Taurine is a semi-essential amino acid in mammals and has been shown to be a potent endogenous antioxidant. The kidney plays a pivotal role in maintaining the balance of taurine. However, the mechanisms underlying the protective effects of taurine against oxLDL-induced injury in renal epithelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effects of taurine on human proximal tubular epithelial (HK-2) cells exposed to oxLDL and explored the related mechanisms. We observed that oxLDL increased the contents of ROS and of malondialdehyde (MDA), which is a lipid peroxidation by-product that acts as an indicator of the cellular oxidation status. In addition, oxLDL induced cell death and apoptosis in HK-2 cells. Pretreatment with taurine at 100 ?M significantly attenuated the oxLDL-induced cytotoxicity. We determined that oxLDL triggered the phosphorylation of ERK and, in turn, the activation of p53 and other apoptosis-related events, including calcium accumulation, destabilization of the mitochondrial permeability and disruption of the balance between pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins. The malfunctions induced by oxLDL were effectively blocked by taurine. Thus, our results suggested that taurine exhibits potential therapeutic activity by preventing oxLDL-induced nephrotoxicity. The inhibition of oxLDL-induced epithelial apoptosis by taurine was at least partially due to its anti-oxidant activity and its ability to modulate the ERK and p53 apoptotic pathways.
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Absence of estrogen receptor alpha (ESR1) gene amplification in a series of breast cancers in Taiwan.
Virchows Arch.
PUBLISHED: 02-05-2014
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Immunohistochemical expression of ER?, encoded by the ESR1 (estrogen receptor 1) gene located at 6q25.1, is the most important determinant of responsiveness to endocrine therapy in breast cancer. The prevalence and significance of ESR1 amplification in breast cancer remain controversial. We set out to assess ESR1 status and its relevance in breast cancer in Taiwan. We tested tissue samples from 311 invasive carcinomas in a tissue microarray for ESR1 status by fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH). In order to examine its association with ER? and ESR1 status, HER2 status was determined by FISH. Of the carcinomas, 58.8 % (183/311) was ER? positive. None of the carcinomas showed amplification of ESR1 by either method, whereas 24.1 % (75/311) of the carcinomas harbored HER2 amplification. Of the carcinomas, 9.6 % (26/301) showed ESR1 gain (1.3???ratio ESR1/chromosome 6?
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Primary and secondary photodynamics of the violet/orange dual-cysteine NpF2164g3 cyanobacteriochrome domain from Nostoc punctiforme.
Biochemistry
PUBLISHED: 02-03-2014
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Cyanobacteriochromes (CBCRs) are cyanobacterial photoreceptors distantly related to phytochromes. Like phytochromes, CBCRs photointerconvert between two photostates that accompany photoisomerization of their bilin chromophores. While phytochromes typically exhibit red/far-red photocycles, CBCR photocycles are much more diverse, spanning the near-ultraviolet and the entire visible region. All CBCRs described to date have a conserved Cys residue covalently attached to the linear tetrapyrrole (bilin) chromophore; two CBCR subfamilies also exploit a second thioether linkage to the chromophore for detection of near-ultraviolet to blue light. Here, we present the photodynamic analysis of the insert-Cys CBCR NpF2164g3, a representative of the second class of two-cysteine CBCRs. Using broadband transient absorption pump-probe spectroscopy, we characterize the primary (100 fs to 10 ns) and secondary (10 ns to 1 ms) photodynamics in both directions, examining photodynamics over nine decades of time. Primary isomerization dynamics occur on a ~10 ps time scale for both forward and reverse reactions. In contrast to previous studies on Tlr0924, a representative of the other class of two-cysteine CBCRs, formation and elimination of the second linkage are slower than the 1 ms experimental range probed here. These results extend our understanding of dual-cysteine CBCR photocycles in the phytochrome superfamily.
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Reliable protocols for whole-mount fluorescent in situ hybridization (FISH) in the pea aphid Acyrthosiphon pisum: a comprehensive survey and analysis.
Insect Sci.
PUBLISHED: 01-15-2014
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RNA in situ hybridization (ISH), including chromogenic ISH (CISH) and fluorescent ISH (FISH), has become a powerful tool for revealing the spatial distribution of gene transcripts in model organisms. Previously, we developed a robust protocol for whole-mount RNA CISH in the pea aphid Acyrthosiphon pisum, an emerging insect genomic model. In order to improve the resolving capacity of gene detection, we comprehensively surveyed current protocols of whole-mount RNA-FISH and developed protocols that allow, using confocal microscopy, clearer visualization of target messenger RNAs (mRNAs) - including those subcellularly localized and those with spatially overlapping expression. We find that Fast dye-based substrate fluorescence (SF), tyramide signal amplification (TSA), and TSA Plus all enable identifying gene expression thanks to multiplex amplification of fluorescent signals. By contrast, methods of direct fluorescence (DF) do not allow visualizing signals. Detection of a single gene target was achieved with SF and TSA Plus for most mRNAs, whereas TSA only allowed visualization of abundant transcripts such as Apvas1 and Appiwi2 in the germ cells. For detection of multiple gene targets using double FISH, we recommend: (i) TSA/TSA, rather than TSA Plus/TSA Plus for colocalized mRNAs abundantly expressed in germ cells, as proteinase K treatment can be omitted; and (ii) SF/TSA Plus for other gene targets such as Apen1 and Apen2 as inactivation of enzyme conjugates is not required. SF/SF is not ideal for double FISH experiments due to signal blurring. Based on these new conditions for RNA-FISH, we have obtained a better understanding of germline specification and embryonic segmentation in the pea aphid. We anticipate that the RNA-FISH protocols for the pea aphid may also be used for other aphids and possibly other insect species, thus expanding the range of species from which useful insights into development and evolution may be obtained.
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A concerted transfer hydrogenolysis: 1,3,2-diazaphospholene-catalyzed hydrogenation of N=N bond with ammonia-borane.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-06-2014
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1,3,2-diazaphospholenes catalyze metal-free transfer hydrogenation of a N=N double bond using ammonia-borane under mild reaction conditions, thus allowing access to various hydrazine derivatives. Kinetic and computational studies revealed that the rate-determining step involves simultaneous breakage of the B-H and N-H bonds of ammonia-borane. The reaction is therefore viewed as a concerted type of hydrogenolysis.
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Multi-step formation of a hemifusion diaphragm for vesicle fusion revealed by all-atom molecular dynamics simulations.
Biochim. Biophys. Acta
PUBLISHED: 01-04-2014
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Membrane fusion is essential for intracellular trafficking and virus infection, but the molecular mechanisms underlying the fusion process remain poorly understood. In this study, we employed all-atom molecular dynamics simulations to investigate the membrane fusion mechanism using vesicle models which were pre-bound by inter-vesicle Ca(2+)-lipid clusters to approximate Ca(2+)-catalyzed fusion. Our results show that the formation of the hemifusion diaphragm for vesicle fusion is a multi-step event. This result contrasts with the assumptions made in most continuum models. The neighboring hemifused states are separated by an energy barrier on the energy landscape. The hemifusion diaphragm is much thinner than the planar lipid bilayers. The thinning of the hemifusion diaphragm during its formation results in the opening of a fusion pore for vesicle fusion. This work provides new insights into the formation of the hemifusion diaphragm and thus increases understanding of the molecular mechanism of membrane fusion. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
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Peliosis hepatis complicated by portal hypertension following renal transplantation.
World J. Gastroenterol.
PUBLISHED: 01-02-2014
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Peliosis hepatis (PH) is a vascular lesion of the liver that mimics a hepatic tumor. PH is often associated with underlying conditions, such as chronic infection and tumor malignancies, or with the use of anabolic steroids, immunosuppressive drugs, and oral contraceptives. Most patients with PH are asymptomatic, but some present with abdominal distension and pain. In some cases, PH may induce intraperitoneal hemorrhage and portal hypertension. This study analyzed a 46-year-old male who received a transplanted kidney nine years prior and had undergone long-term immunosuppressive therapy following the renal transplantation. The patient experienced progressive abdominal distention and pain in the six months prior to this study. Initially, imaging studies revealed multiple liver tumor-like abnormalities, which were determined to be PH by pathological analysis. Because the hepatic lesions were progressively enlarged, the patient suffered from complications related to portal hypertension, such as intense ascites and esophageal varices bleeding. Although the patient was scheduled to undergo liver transplantation, he suffered hepatic failure and died prior to availability of a donor organ.
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Posterior localization of ApVas1 positions the preformed germ plasm in the sexual oviparous pea aphid Acyrthosiphon pisum.
Evodevo
PUBLISHED: 01-01-2014
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Germline specification in some animals is driven by the maternally inherited germ plasm during early embryogenesis (inheritance mode), whereas in others it is induced by signals from neighboring cells in mid or late development (induction mode). In the Metazoa, the induction mode appears as a more prevalent and ancestral condition; the inheritance mode is therefore derived. However, regarding germline specification in organisms with asexual and sexual reproduction it has not been clear whether both strategies are used, one for each reproductive phase, or if just one strategy is used for both phases. Previously we have demonstrated that specification of germ cells in the asexual viviparous pea aphid depends on a preformed germ plasm. In this study, we extended this work to investigate how germ cells were specified in the sexual oviparous embryos, aiming to understand whether or not developmental plasticity of germline specification exists in the pea aphid.
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Targeting the biophysical properties of the myeloma initiating cell niches: a pharmaceutical synergism analysis using multi-scale agent-based modeling.
PLoS ONE
PUBLISHED: 01-01-2014
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Multiple myeloma, the second most common hematological cancer, is currently incurable due to refractory disease relapse and development of multiple drug resistance. We and others recently established the biophysical model that myeloma initiating (stem) cells (MICs) trigger the stiffening of their niches via SDF-1/CXCR4 paracrine; The stiffened niches then promote the colonogenesis of MICs and protect them from drug treatment. In this work we examined in silico the pharmaceutical potential of targeting MIC niche stiffness to facilitate cytotoxic chemotherapies. We first established a multi-scale agent-based model using the Markov Chain Monte Carlo approach to recapitulate the niche stiffness centric, pro-oncogenetic positive feedback loop between MICs and myeloma-associated bone marrow stromal cells (MBMSCs), and investigated the effects of such intercellular chemo-physical communications on myeloma development. Then we used AMD3100 (to interrupt the interactions between MICs and their stroma) and Bortezomib (a recently developed novel therapeutic agent) as representative drugs to examine if the biophysical properties of myeloma niches are drugable. Results showed that our model recaptured the key experimental observation that the MBMSCs were more sensitive to SDF-1 secreted by MICs, and provided stiffer niches for these initiating cells and promoted their proliferation and drug resistance. Drug synergism analysis suggested that AMD3100 treatment undermined the capability of MICs to modulate the bone marrow microenvironment, and thus re-sensitized myeloma to Bortezomib treatments. This work is also the first attempt to virtually visualize in 3D the dynamics of the bone marrow stiffness during myeloma development. In summary, we established a multi-scale model to facilitate the translation of the niche-stiffness centric myeloma model as well as experimental observations to possible clinical applications. We concluded that targeting the biophysical properties of stem cell niches is of high clinical potential since it may re-sensitize tumor initiating cells to chemotherapies and reduce risks of cancer relapse.
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Design of an Amide N-Glycoside Derivative of ?-Glucogallin: A Stable, Potent, and Specific Inhibitor of Aldose Reductase.
J. Med. Chem.
PUBLISHED: 12-23-2013
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?-Glucogallin (BGG), a major component of the Emblica officinalis medicinal plant, is a potent and selective inhibitor of aldose reductase (AKR1B1). New linkages (ether/triazole/amide) were introduced via high yielding, efficient syntheses to replace the labile ester, and an original two-step (90%) preparation of BGG was developed. Inhibition of AKR1B1was assessed in vitro and using transgenic lens organ cultures, which identified the amide linked glucoside (BGA) as a stable, potent, and selective therapeutic lead toward the treatment of diabetic eye disease.
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1,6- and 1,7-regioisomers of asymmetric and symmetric perylene bisimides: synthesis, characterization and optical properties.
Molecules
PUBLISHED: 11-25-2013
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The 1,6- and 1,7-regioisomers of dinitro- (1,6-A and 1,7-A) and diamino-substituted perylene bisimides (1,6-B and 1,7-B), and 1-amino-6-nitro- and 1-amino-7-nitroperylene bisimides (1,6-C and 1,7-C) were synthesized. The 1,6-A and 1,7-A regioisomers were successfully separated by high performance liquid chromatography and characterized by 500 MHz 1H-NMR spectroscopy, and subsequently, their reduction which afforded the corresponding diaminoperylene bisimides 1,6-B and 1,7-B, respectively. On the other hand, the monoreduction of 1,6-A and 1,7-A, giving the asymmetric 1-amino-6-nitro (1,6-C) and 1-amino-7-nitroperylene bisimides (1,7-C), respectively, can be performed by shortening the reaction time from 6 h to 1 h. This is the first time the asymmetric 1,6-disubstituted perylene bisimide 1,6-C is obtained in pure form. The photophysical properties of 1,6-A and 1,7-A were found to be almost the same. However, the regioisomers 1,6-C and 1,7-C, as well as 1,6-B and 1,7-B, exhibit significant differences in their optical characteristics. Time-dependent density functional theory calculations performed on these dyes are reported in order to rationalize their electronic structure and absorption spectra.
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Melatonin improves neuroplasticity by upregulating the growth-associated protein 43 (GAP-43) and NMDAR-post-synaptic density-95 (PSD95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral isch
J. Pineal Res.
PUBLISHED: 11-04-2013
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Recent evidence shows that the NMDAR-post-synaptic density-95 (PSD95), growth-associated protein 43 (GAP-43) and matrix metalloproteinase-9 (MMP-9) protein enhance neuroplasticity at the subacute stage of stroke. Here, we evaluated whether melatonin would modulate the PSD95, GAP-43 and MMP-9 proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to experimental stroke. Adult male Sprague-Dawley rats were treated with melatonin (5 mg/kg) or vehicle at reperfusion onset after transient occlusion of the right middle cerebral artery (tMCAO) for 90 min. Animals were euthanized for Western immunoblot analyses for the PSD-95 and GAP-43 proteins and gelatin zymography for the MMP-9 activity at 7-day post-insult. Another set of animals was sacrificed for histologic and Golgi-Cox-impregnated sections at 28 days post-insult. In cultured neurons exposed to glutamate excitotoxicity, melatonin significantly up-regulated the GAP-43 and PSD-95 expressions and improved dendritic aborizations (P < 0.05, respectively). Relative to controls, melatonin-treated stroke animals caused a significant improvement of GAP-43 and PSD-95 expressions as well as the MMP-9 activity in the ischemic brain (P < 0.05). Consequently, melatonin also significantly promoted the dendritic spine density and reduced infarction in the ischemic brain, and improved neurobehaviors as well at 28 days post-insult (P < 0.05, respectively). Together, melatonin upregulates GAP-43, PSD-95 and MMP-9 proteins, which likely accounts for its actions to improve neuroplasticity in cultured neurons exposed to glutamate excitotoxicity, and to enhance long-term neuroprotection, neuroplasticity and brain remodeling in stroke rats. This article is protected by copyright. All rights reserved.
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Unraveling the Primary Isomerization Dynamics in Cyanobacterial Phytochrome Cph1 with Multi-pulse Manipulations.
J Phys Chem Lett
PUBLISHED: 10-22-2013
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The ultrafast mechanisms underlying the initial photoisomerization (Pr ? Lumi-R) in the forward reaction of the cyanobacterial photoreceptor Cph1 were explored with multipulse pump-dump-probe transient spectroscopy. A recently postulated multi-population model was used to fit the transient pump-dump-probe and dump-induced depletion signals. We observed dump-induced depletion of the Lumi-R photoproduct, demonstrating that photoisomerization occurs via evolution on both the excited- and ground-state electronic surfaces. Excited-state equilibrium was not observed, as shown via the absence of a dump-induced excited-state "Le Châtelier redistribution" of excited-state populations. The importance of incorporating the inhomogeneous dynamics of Cph1 in interpreting measured transient data is discussed.
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Surface passivation of efficient nanotextured black silicon solar cells using thermal atomic layer deposition.
ACS Appl Mater Interfaces
PUBLISHED: 09-30-2013
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Efficient nanotextured black silicon solar cells passivated by an Al2O3 layer are demonstrated. The broadband antireflection of the nanotextured black silicon solar cells was provided by fabricating vertically aligned silicon nanowire (SiNW) arrays on the n(+) emitter. A highly conformal Al2O3 layer was deposited upon the SiNW arrays by the thermal atomic layer deposition (ALD) based on the multiple pulses scheme. The nanotextured black silicon wafer covered with the Al2O3 layer exhibited a low total reflectance of ?1.5% in a broad spectrum from 400 to 800 nm. The Al2O3 passivation layer also contributes to the suppressed surface recombination, which was explored in terms of the chemical and field-effect passivation effects. An 8% increment of short-circuit current density and 10.3% enhancement of efficiency were achieved due to the ALD Al2O3 surface passivation and forming gas annealing. A high efficiency up to 18.2% was realized in the ALD Al2O3-passivated nanotextured black silicon solar cells.
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Shrimp that have received carrageenan via immersion and diet exhibit immunocompetence in phagocytosis despite a post-plateau in immune parameters.
Fish Shellfish Immunol.
PUBLISHED: 09-28-2013
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The effect of carrageenan on the immune response of white shrimp Litopenaeus vannamei, was studied in vitro and in vivo. Shrimp haemocytes receiving carrageenan at 1 mg ml(-1) experienced change in cell size, reduction in cell viability, increase in PO activity, serine proteinase activity, and RB in vitro. Shrimp received carrageenan via immersion at 200, 400 and 600 mg L(-1) after 3 h and orally at 0.5, 1.0 and 2.0 g kg(-1) after 3 weeks showed higher proliferation of haematopoietic tissues (HPTs) together with increases in haemocyte count and other immune parameters. Shrimp that fed a diet containing carrageenan at 0.5 g kg(-1) after 3 weeks significantly up-regulated gene expressions of several immune-related proteins. The immune parameters of shrimp that received carrageenan via immersion and orally increased to a plateau after 3 h and after 3 weeks, but decreased after 5 h and 6 weeks, respectively. Phagocytosis and clearance of Vibrio alginolyticus remained high in shrimp that had received carrageenan via immersion after 5 h and orally after 6 weeks, respectively. Resistances of shrimp against V. alginolyticus and white spot syndrome virus were higher over 24-144 h and 72-144 h, respectively in shrimp that received carrageenan at 600 mg L(-1) via immersion after 3 and 5 h. It was concluded that carrageenan effectively triggers an innate immunity in vitro, and increases mitotic index of HPT, immune parameters, gene expressions and resistance against pathogens in vivo. Shrimp received carrageenan via immersion and orally exhibited immunocompetence in phagocytosis and clearance of V. alginolyticus, and resistance to pathogen despite the trend in immune parameters to recover to background values.
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Human Interleukin 23 Receptor Induces Cell Apoptosis in Mammalian Cells by Intrinsic Mitochondrial Pathway Associated with the Down-Regulation of RAS/Mitogen-Activated Protein Kinase and Signal Transducers and Activators of Transcription factor 3 Signalin
Int J Mol Sci
PUBLISHED: 09-01-2013
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The composition of IL-23R complex is similar to that of the IL-12 receptor (IL-12R) complex with a shared IL-12R-?1 chain. The IL-12R-?1 heterodimerizes with IL-23R and IL-12R-?2 to form IL-23R and IL-12R complexes, respectively. The IL-12R-?2 has been shown to function as a tumor suppressor gene and apoptotic inducer. However, whether IL-23R also functions in cell apoptosis is currently unknown. In this study, we demonstrate for the first time that overexpression of IL-23R markedly induces cell apoptosis in both 293ET and HeLa cells. The activations of caspase 3 and caspase 9 are induced by IL-23R. Mechanistic study reveals that IL-23R markedly inhibits RAS/MAPK and STAT3 but not STAT1 and PI-3K/Akt signaling pathways in both 293ET and HeLa cells. Overexpression of IL-23R significantly up-regulates IL-12R?1 expression but not IL-23? and IL-12? expressions in both cell lines. Therefore, our data strongly indicates that IL-23R is able to induce cell apoptosis by activating the intrinsic mitochondrial pathways associated with the inhibition in RAS/MAPK and STAT3 activations in mammalian cells.
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Elevated circulating levels of tissue factor-positive microvesicles are associated with distant metastasis in lung cancer.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 08-15-2013
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Microvesicles (MV) in the blood stream are associated with distant metastasis in cancer. Platelet or endothelial cell-related MV actively participate in thrombogenesis, which is an important step in cancer metastasis. This study investigated the correlations between MV levels of platelet-poor plasma and distant metastasis in lung cancer.
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Use of endoscopy with narrow-band imaging system in detecting squamous cell carcinoma in oral chronic non-healing ulcers.
Clin Oral Investig
PUBLISHED: 06-26-2013
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This study seeks to analyze the factors associated with the occurrence of squamous cell carcinoma in oral non-healing ulcers for more than 3 weeks and investigate the role of endoscopy with narrow-band imaging system (NBI) in detecting carcinoma in these lesions.
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PET or PET/CT for detection of peritoneal carcinomatosis: a meta-analysis.
Clin Nucl Med
PUBLISHED: 06-26-2013
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The present study assessed the diagnostic performances of (18)F-FDG PET or PET/CT in detecting peritoneal carcinomatosis in patients with cancer.
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Reactive ground-state pathways are not ubiquitous in red/green cyanobacteriochromes.
J Phys Chem B
PUBLISHED: 06-19-2013
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Recent characterization of the red/green cyanobacteriochrome (CBCR) NpR6012g4 revealed a high quantum yield for its forward photoreaction [J. Am. Chem. Soc. 2012, 134, 130-133] that was ascribed to the activity of hidden, productive ground-state intermediates. The dynamics of the pathways involving these ground-state intermediates was resolved with femtosecond dispersed pump-dump-probe spectroscopy, the first such study reported for any CBCR. To address the ubiquity of such second-chance initiation dynamics (SCID) in CBCRs, we examined the closely related red/green CBCR NpF2164g6 from Nostoc punctiforme. Both NpF2164g6 and NpR6012g4 use phycocyanobilin as the chromophore precursor and exhibit similar excited-state dynamics. However, NpF2164g6 exhibits a lower quantum yield of 32% for the generation of the isomerized Lumi-R primary photoproduct, compared to 40% for NpR6012g4. This difference arises from significantly different ground-state dynamics between the two proteins, with the SCID mechanism deactivated in NpF2164g6. We present an integrated inhomogeneous target model that self-consistently fits the pump-probe and pump-dump-probe signals for both forward and reverse photoreactions in both proteins. This work demonstrates that reactive ground-state intermediates are not ubiquitous phenomena in CBCRs.
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The Drosophila GOLPH3 homolog regulates the biosynthesis of heparan sulfate proteoglycans by modulating the retrograde trafficking of exostosins.
Development
PUBLISHED: 05-29-2013
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The exostosin (EXT) genes encode glycosyltransferases required for glycosaminoglycan chain polymerization in the biosynthesis of heparan sulfate proteoglycans (HSPGs). Mutations in the tumor suppressor genes EXT1 and EXT2 disturb HSPG biosynthesis and cause multiple osteochondroma (MO). How EXT1 and EXT2 traffic within the Golgi complex is not clear. Here, we show that Rotini (Rti), the Drosophila GOLPH3, regulates the retrograde trafficking of EXTs. A reduction in Rti shifts the steady-state distribution of EXTs to the trans-Golgi. These accumulated EXTs tend to be degraded and their re-entrance towards the route for polymerizing GAG chains is disengaged. Conversely, EXTs are mislocalized towards the transitional endoplasmic reticulum/cis-Golgi when Rti is overexpressed. Both loss of function and overexpression of rti result in incomplete HSPGs and perturb Hedgehog signaling. Consistent with Drosophila, GOLPH3 modulates the dynamic retention and protein stability of EXT1/2 in mammalian species. Our data demonstrate that GOLPH3 modulates the activities of EXTs, thus implicating a putative role for GOLPH3 in the formation of MO.
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WWP1 gene is a potential molecular target of human oral cancer.
Oral Surg Oral Med Oral Pathol Oral Radiol
PUBLISHED: 05-02-2013
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This study investigates the oncogenic role of WWP1, an ubiquitin ligase linked to tumor promotion, in oral cancer.
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Precise monitoring of chemical changes through localization analysis of dynamic spectra (LADS).
Appl Spectrosc
PUBLISHED: 04-30-2013
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We present a method for monitoring subtle (sub-wavenumber) dynamics within time-varying spectra. Peak fitting is performed for large numbers of spectra in a series, allowing for monitoring time evolutions of peak positions with high precision and confidence. Sub-wavenumber peak shifts due to physical or chemical changes in the sample can be monitored and their temporal evolution characterized. In surface-enhanced Raman scattering experiments, we were able to distinguish between slow photo-damage and fast conformational change dynamics. Fluctuations in peak positions of Raman spectra recorded from a single yeast cell indicated that no significant irreversible photo-damage occurred, but these fluctuations suggest changes in the trapping conditions or biochemical changes associated with the cellular machinery in the cell. The technique is particularly suitable for applications where dynamics of spectra are of interest.
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Influence of calcium hydroxide dressing and acid etching on the push-out bond strengths of three luting resins to root canal dentin.
Clin Oral Investig
PUBLISHED: 04-23-2013
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OBJECTIVES: This study aims to investigate the effects of calcium hydroxide (Ca(OH)2) dressing in root canals and the effects of subsequent acid etching on the adhesion of luting resins to root canals. MATERIALS AND METHODS: Root specimens were prepared from extracted human permanent molars. Specimen canals were (1) filled with etch-and-rinse (Nexus® third generation (NX3)) and two self-adhesive (RelyX Unicem, Maxcem Elite) luting resins, respectively; (2) dressed with Ca(OH)2 before Ca(OH)2 removal and luting resin filling; (3) dressed with Ca(OH)2 before Ca(OH)2 removal and post-cementation; or (4) treated as described in item (2) except that the canals were further etched with phosphoric acid before luting resin filling. Push-out bond strengths were measured and analyzed using one-way analysis of variance, and Fishers multiple comparison tests provided a follow-up comparison among these four canal treatments. Attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) were used to analyze the specimen surfaces. RESULTS: Ca(OH)2 dressing adversely affected the bond strengths to canal dentin of the three luting resins tested. Acid etching did not increase the bond strengths. Infrared analysis revealed that Ca(OH)2 dressing caused no structural changes on the dentin surface. XPS and SEM analyses revealed Ca(OH)2 remnants as the ultimate chemical cause leading to the decrease in bond strength. CONCLUSIONS: The bond strength of luting resin to dentin was affected by Ca(OH)2 dressing. Acid etching treatment could not increase the bond strength. CLINICAL RELEVANCE: Adhesion of the fiber post to the root canal wall may be compromised after Ca(OH)2 dressing. An effective method for complete removal of Ca(OH)2 dressing or increase of bond strength for luting resin needs to be developed.
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Proapoptotic and TRAIL-sensitizing constituents isolated from Salvia militiorrhiza (Danshen).
J. Biosci. Bioeng.
PUBLISHED: 03-26-2013
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Natural compounds isolated from medicinal plants are invaluable resources for drug discovery. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent unique by its cancer cell-specific proapoptotic action, but its potential is heavily curbed by acquired resistance. We herein reported for the first time the identification of cytotoxic and TRAIL-sensitizing components of Salvia miltiorrhiza (Danshen), a traditional medicinal plant effective for treating cardiovascular disorders. Specifically, we found that the ethanol extract and its group 5 fraction of S. miltiorrhiza showed evident cytotoxicity against the human lung adenocarcinoma cell line A549 and ovarian adenocarcinoma cell line TOV-21G in a concentration-dependent manner. Likewise, a dose-dependent cytotoxicity was exerted by the standard solutions of cryptotanshinone, tanshinone I and tanshinone IIA, the major components of the group 5 fraction, where tanshinone IIA were most potent and displayed an IC?? of 2.00 ± 0.36 ?M and 2.75 ± 0.23 ?M for A549 and TOV-21G, respectively. Induction of apoptosis represents an essential mechanism underlying tanshinone IIA-mediated cytotoxic action, as evidenced by the proteolytic processing of PARP upon tanshinone IIA stimulation and, importantly, a marked rescue of the viability of tanshinone IIA-treated cells when co-treatment with the pan-caspase inhibitor z-VAD-fmk. Noteworthy, stimulation with cryptotanshinone, tanshinone I or tanshinone IIA all effectively potentiated TRAIL to reduce viability and inhibit the colony formation capacity of TRAIL-resistant TOV-21G and SKOV3. Collectively, we revealed the proapoptotic and TRAIL-sensitizing components of S. miltiorrhiza and further implicated the potential of developing these active compounds as monotherapeutic agent or TRAIL-based therapy for cancer chemoprevention or chemotherapy.
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Immunohistochemical study of the Nrf2 pathway in colorectal cancer: Nrf2 expression is closely correlated to Keap1 in the tumor and Bach1 in the normal tissue.
Appl. Immunohistochem. Mol. Morphol.
PUBLISHED: 03-05-2013
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Oxidative stress is a contributing factor in the carcinogenesis of colorectal cancer. The Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] pathway is one of the major cellular defense mechanisms against oxidative stress. This study investigated the expression of the Nrf2 pathway in colorectal cancer. Formalin-fixed paraffin-embedded tissue arrays consisting of the tumor, adjacent normal, and distant normal tissues from the resected specimens of 83 colorectal cancer patients were subjected to immunohistochemical (IHC) staining with antibodies against Nrf2, kelch-like ECH-associated protein 1 (Keap1), p21, P62, Parkinson protein 7 (Park7), prohibitin, BTB and CNC homology 1 (Bach1), CD34 and 8-hydroxy-2-deoxyguanosine (8-OHdG). The mean IHC density of each IHC staining was digitally analyzed. The results showed that molecules of the Nrf2 pathway were actively expressed, with different expression profiles among the tumor and normal tissues. The oxidative stress, represented by the mean IHC staining density of 8-OHdG, did not differ but was correlated with the expressions of different Nrf2 pathway molecules to a varied extent in tumor and normal tissues of colorectal cancer. Keap1 [estimate, 0.49; 95% confidence interval (CI), 0.19-0.79] and Bach1 (estimate, 0.24; 95% CI, 0.11-0.38) were significant predictors for the expression of 8-OHdG and had the closest proximity to Nrf2 in the cluster dendrogram of the tumor and distant normal tissues, respectively. Advanced stage (estimate, 14.9; 95% CI, 2.99-26.8) and current smoker (estimate, 15.6; 95% CI, 1.92-29.3) were significant predictors with high estimates for Bach1 in the adjacent and distant normal tissues, respectively. In colorectal cancer, the molecules of the Nrf2 pathway have different expression profiles and a difference in their importance, especially Keap1 and Bach1, related to Nrf2 and oxidative stress among tumor and normal tissues.
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Cardiopulmonary Profile in Streptozotocin-Induced Type 1 Diabetic Rats during Systemic Endotoxemia.
J Diabetes Res
PUBLISHED: 02-25-2013
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This study was designed to determine the severity of cardiopulmonary dysfunction during systemic endotoxemia in type 1 diabetes. Thirty-two adult male Wistar rats were randomly assigned to a control group or to a group treated with streptozotocin (STZ) to create an animal model of type 1 diabetes. Survival time and cardiovascular parameters were continually monitored in urethane anaesthetized animals receiving intravenous infusion of endotoxin (lipopolysaccharide (LPS)) or saline. We also determined arterial blood gases, lung injury, and tumor necrosis factor-alpha (TNF- ? ) levels in serum and bronchoalveolar lavage fluid. Before LPS administration, the mean arterial pressure in STZ rats was significantly higher than that in normal rats. After LPS injection, the heart rate drop significantly in STZ rats than that in the control group. Also, the increased levels of TNF- ? in serum and lavage fluid after LPS treatment were significantly higher in STZ rats than those in normal rats. Survival time in STZ rats was shorter than that in normal rats after LPS application. Albumin content, wet/dry weight ratio of lung, and lung injury were indistinguishable between STZ and normal rats. These results indicate that the cardiopulmonary change which occurs during LPS-induced endotoxemia is minor in STZ-induced diabetic rats.
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Choroid metastases revealing primary clear cell adenocarcinoma of the lung effectively treated with cisplatin and pemetrexed: a case report.
J Med Case Rep
PUBLISHED: 02-24-2013
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The aim of the present report was to draw the attention of oncologists to the importance of prompt diagnosis of primary clear cell adenocarcinoma of the lung, which allows early initiation of treatment to maintain quality of life.
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Subamolide B Isolated from Medicinal Plant Cinnamomum subavenium Induces Cytotoxicity in Human Cutaneous Squamous Cell Carcinoma Cells through Mitochondrial and CHOP-Dependent Cell Death Pathways.
Evid Based Complement Alternat Med
PUBLISHED: 02-05-2013
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Subamolide B is a butanolide isolated from Cinnamomum subavenium, a medicinal plant traditionally used to treat various ailments including carcinomatous swelling. We herein reported for the first time that subamolide B potently induced cytotoxicity against diverse human skin cancer cell lines while sparing nonmalignant cells. Mechanistic studies on human cutaneous squamous cell carcinoma (SCC) cell line SCC12 highlighted the involvement of apoptosis in subamolide B-induced cytotoxicity, as evidenced by the activation of caspases-8, -9, -4, and -3, the increase in annexin V-positive population, and the partial restoration of cell viability by cotreatment with the pan-caspase inhibitor z-VAD-fmk. Additionally, subamolide B evoked cell death pathways mediated by FasL/Fas, mitochondria, and endoplasmic reticulum (ER) stress, as supported by subamolide B-induced FasL upregulation, BCL-2 suppression/cytosolic release of cytochrome c, and UPR activation/CHOP upregulation, respectively. Noteworthy, ectopic expression of c-FLIPL or dominant-negative mutant of FADD failed to impair subamolide B-induced cytotoxicity, whereas BCL-2 overexpression or CHOP depletion greatly rescued subamolide B-stimulated cells. Collectively, these results underscored the central role of mitochondrial and CHOP-mediated cell death pathways in subamolide B-induced cytotoxicity. Our findings further implicate the potential of subamolide B for cutaneous SCC therapy or as a lead compound for developing novel chemotherapeutic agents.
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IL28B polymorphism correlates with active hepatitis in patients with HBeAg-negative chronic hepatitis B.
PLoS ONE
PUBLISHED: 01-29-2013
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The clinical relevance of single nucleotide polymorphisms (SNPs) near the IL28B gene is controversial in patients with hepatitis B virus (HBV) infection. This study aimed to investigate the role of viral and host factors, including IL28B genotypes, in the natural course of chronic hepatitis B (CHB).
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Molecular mechanism of Ca(2+)-catalyzed fusion of phospholipid micelles.
Biochim. Biophys. Acta
PUBLISHED: 01-24-2013
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Although membrane fusion plays key roles in intracellular trafficking, neurotransmitter release, and viral infection, its underlying molecular mechanism and its energy landscape are not well understood. In this study, we employed all-atom molecular dynamics simulations to investigate the fusion mechanism, catalyzed by Ca(2+) ions, of two highly hydrated 1-palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE) micelles. This simulation system mimics the small contact zone between two large vesicles at which the fusion is initiated. Our simulations revealed that Ca(2+) ions are capable of catalyzing the fusion of POPE micelles; in contrast, we did not observe close contact of the two micelles in the presence of only Na(+) or Mg(2+) ions. Determining the free energy landscape of fusion allowed us to characterize the underlying molecular mechanism. The Ca(2+) ions play a key role in catalyzing the micelle fusion in three aspects: creating a more-hydrophobic surface on the micelles, binding two micelles together, and enhancing the formation of the pre-stalk state. In contrast, Na(+) or Mg(2+) ions have relatively limited effects. Effective fusion proceeds through sequential formation of pre-stalk, stalk, hemifused-like, and fused states. The pre-stalk state is the state featuring lipid tails exposed to the inter-micellar space; its formation is the rate-limiting step. The stalk state is the state where a localized hydrophobic core is formed connecting two micelles; its formation occurs in conjunction with water expulsion from the inter-micellar space. This study provides insight into the molecular mechanism of fusion from the points of view of energetics, structure, and dynamics.
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Identification of SNP-containing regulatory motifs in the myelodysplastic syndromes model using SNP arrays and gene expression arrays.
Chin J Cancer
PUBLISHED: 01-18-2013
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Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies--single nucleotide polymor-phism(SNP) array and gene expression array--with gene motifs considered transcription factor-binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on co-regulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.
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Discovering transcription and splicing networks in myelodysplastic syndromes.
PLoS ONE
PUBLISHED: 01-01-2013
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More and more transcription factors and their motifs have been reported and linked to specific gene expression levels. However, focusing only on transcription is not sufficient for mechanism research. Most genes, especially in eukaryotes, are alternatively spliced to different isoforms. Some of these isoforms increase the biodiversity of proteins. From this viewpoint, transcription and splicing are two of important mechanisms to modulate expression levels of isoforms. To integrate these two kinds of regulation, we built a linear regression model to select a subset of transcription factors and splicing factors for each co-expressed isoforms using least-angle regression approach. Then, we applied this method to investigate the mechanism of myelodysplastic syndromes (MDS), a precursor lesion of acute myeloid leukemia. Results suggested that expression levels of most isoforms were regulated by a set of selected regulatory factors. Some of the detected factors, such as EGR1 and STAT family, are highly correlated with progression of MDS. We discovered that the splicing factor SRSF11 experienced alternative splicing switch, and in turn induced different amino acid sequences between MDS and controls. This splicing switch causes two different splicing mechanisms. Polymerase Chain Reaction experiments also confirmed that one of its isoforms was over-expressed in MDS. We analyzed the regulatory networks constructed from the co-expressed isoforms and their regulatory factors in MDS. Many of these networks were enriched in the herpes simplex infection pathway which involves many splicing factors, and pathways in cancers and acute or chronic myeloid leukemia.
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Aliskiren attenuates steatohepatitis and increases turnover of hepatic fat in mice fed with a methionine and choline deficient diet.
PLoS ONE
PUBLISHED: 01-01-2013
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Activation of the renin-angiotensin-system is known to play a role in nonalcoholic steatohepatitis. Renin knockout mice manifest decreased hepatic steatosis. Aliskiren is the first direct renin inhibitor to be approved for clinical use. Our study aims to evaluate the possible therapeutic effects and mechanism of the chronic administration of aliskiren in a dietary steatohepatitis murine model.
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Vaccination enhances early immune responses in white shrimp Litopenaeus vannamei after secondary exposure to Vibrio alginolyticus.
PLoS ONE
PUBLISHED: 01-01-2013
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Recent work suggested that the presence of specific memory or some form of adaptive immunity occurs in insects and shrimp. Hypervariable pattern recognition molecules, known as Down syndrome cell adhesion molecules, are able to mount specific recognition, and immune priming in invertebrates. In the present study, we attempted to understand the immune response pattern of white shrimp Litopenaeus vannamei which received primary (PE) and secondary exposure (SE) to Vibrio alginolyticus.
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Dual-colour chromogenic in-situ hybridization is a potential alternative to fluorescence in-situ hybridization in HER2 testing.
Histopathology
PUBLISHED: 11-19-2011
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Dual-colour chromogenic in-situ hybridization (dc-CISH) is an emerging methodology for characterizing genomic alterations. This study was aimed at evaluating the performance of a dc-CISH kit (ZytoVision) in determining human epidermal growth factor receptor 2 (HER2) status in breast cancer.
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The evolution of academic performance in emergency medicine journals: viewpoint from 2000 to 2009 journal citation reports.
Acad Emerg Med
PUBLISHED: 08-17-2011
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Emergency medicine (EM) is a young but rapidly growing field. An evaluation of academic performance and the growing impact of EM journals would help to elucidate the increase in the number of EM scientific studies. The authors used the Journal Citation Reports (JCR) database to investigate the scientific achievements of EM journals in the past 10 years.
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De novo malignant solitary fibrous tumor of the kidney.
Diagn Pathol
PUBLISHED: 08-10-2011
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The kidney is a relatively infrequent site for solitary fibrous tumor (SFT). Among the previously reported cases, only two cases of malignant renal SFT developing via dedifferentiation from a pre-existing benign SFT have been reported. Here we reported a case of de novo malignant renal SFT clinically diagnosed as renal cell carcinoma in a 50-year-old woman. The tumor was circumscribed but unencapsulated and showed obvious hemorrhagic necrosis. Microscopically, the tumor was composed of patternless sheets of alternating hypercellular and hypocellular areas of spindle cells displaying mild to moderate nuclear atypia, frequent mitoses up to 8 per 10 high power fields, and a 20% Ki-67 proliferative index. Immunohistochemical studies revealed reactivity for CD34, CD99 and vimentin, with no staining for all other markers, confirming the diagnosis of SFT. No areas of dedifferentiation were seen after extensive sampling. Based on the pathologic and immunohistochemical features, a diagnosis of de novo malignant renal SFT was warranted. Our report expands the spectrum of malignant progression in renal SFTs. Even though this patient has been disease-free for 30 months, long-term follow-up is still mandatory.
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TaqMan real-time PCR for detection and quantitation of squash leaf curl virus in cucurbits.
J. Virol. Methods
PUBLISHED: 07-19-2011
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A real-time PCR assay based on the TaqMan chemistry was developed for reliable detection and quantitation of the squash leaf curl virus (SLCV) in melon and squash plants. This method was highly specific to SLCV and it was about one thousand times more sensitive than the conventional PCR method. The protocol of the real-time PCR established in this study enabled detection of as little as 10(2) copies of SLCV DNA with CP gene as the target. This TaqMan real-time PCR assay for detection and quantitation of SLCV would be a useful tool for application in quarantine and certification of SLCV in cucurbits as well as in the research of disease resistance and epidemiology.
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Initially twisted pi cell fabricated using liquid crystal-silica colloidal dispersions.
Opt Express
PUBLISHED: 07-13-2011
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We demonstrate an initially twisted pi cell fabricated by doping silica nanoparticles into the conventional pi cell. With AC high voltage, the director distortion of the liquid crystals (LCs) near the substrate surface creates a lifting force, which moves the silica nanoparticles toward the substrate surfaces. The accumulated silica nanoparticles on the substrate surfaces stabilize the LCs at the twisted pi state when the AC high voltage is turned off. The formed twisted pi state is permanent. The operation voltage and the response time of the initially twisted pi cell are less than those of the conventional pi cell.
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Expansion of genes encoding piRNA-associated argonaute proteins in the pea aphid: diversification of expression profiles in different plastic morphs.
PLoS ONE
PUBLISHED: 07-04-2011
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Piwi-interacting RNAs (piRNAs) are known to regulate transposon activity in germ cells of several animal models that propagate sexually. However, the role of piRNAs during asexual reproduction remains almost unknown. Aphids that can alternate sexual and asexual reproduction cycles in response to seasonal changes of photoperiod provide a unique opportunity to study piRNAs and the piRNA pathway in both reproductive modes. Taking advantage of the recently sequenced genome of the pea aphid Acyrthosiphon pisum, we found an unusually large lineage-specific expansion of genes encoding the Piwi sub-clade of Argonaute proteins. In situ hybridisation showed differential expressions between the duplicated piwi copies: while Api-piwi2 and Api-piwi6 are "specialised" in germ cells their most closely related copy, respectively Api-piwi5 and Api-piwi3, are expressed in the somatic cells. The differential expression was also identified in duplicated ago3: Api-ago3a in germ cells and Api-ago3b in somatic cells. Moreover, analyses of expression profiles of the expanded piwi and ago3 genes by semi-quantitative RT-PCR showed that expressions varied according to the reproductive types. These specific expression patterns suggest that expanded aphid piwi and ago3 genes have distinct roles in asexual and sexual reproduction.
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Prodigiosin inhibits gp91(phox) and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia-ischemia.
Toxicol. Appl. Pharmacol.
PUBLISHED: 06-28-2011
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This study aimed to explore the mechanisms by which prodigiosin protects against hypoxia-induced oxidative/nitrosative brain injury induced by middle cerebral artery occlusion/reperfusion (MCAo/r) injury in mice. Hypoxia in vitro was modeled using oxygen-glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone MCAo/r injury with prodigiosin (10 and 100?g/kg, i.v.) at 1h after hypoxia ameliorated MCAo/r-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. MCAo/r induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (gp91(phox)), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b leukocytes due to breakdown of blood-brain barrier (BBB) by activation of nuclear factor-kappa B (NF-?B). All these changes were significantly diminished by prodigiosin. In BV-2 cells, OGD induced ROS and nitric oxide production by up-regulating gp91(phox) and iNOS via activation of the NF-?B pathway, and these changes were suppressed by prodigiosin. In conclusion, our results indicate that prodigiosin reduces gp91(phox) and iNOS expression possibly by impairing NF-?B activation. This compromises the activation of microglial and/or inflammatory cells, which then, in turn, mediates prodigiosins protective effect in the MCAo/r mice.
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Waist-to-height ratio, waist circumference, and body mass index as indices of cardiometabolic risk among 36,642 Taiwanese adults.
Eur J Nutr
PUBLISHED: 06-17-2011
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We aimed to investigate the association of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with cardiometabolic risk.
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Real-time gait cycle parameter recognition using a wearable accelerometry system.
Sensors (Basel)
PUBLISHED: 06-13-2011
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This paper presents the development of a wearable accelerometry system for real-time gait cycle parameter recognition. Using a tri-axial accelerometer, the wearable motion detector is a single waist-mounted device to measure trunk accelerations during walking. Several gait cycle parameters, including cadence, step regularity, stride regularity and step symmetry can be estimated in real-time by using autocorrelation procedure. For validation purposes, five Parkinsons disease (PD) patients and five young healthy adults were recruited in an experiment. The gait cycle parameters among the two subject groups of different mobility can be quantified and distinguished by the system. Practical considerations and limitations for implementing the autocorrelation procedure in such a real-time system are also discussed. This study can be extended to the future attempts in real-time detection of disabling gaits, such as festinating or freezing of gait in PD patients. Ambulatory rehabilitation, gait assessment and personal telecare for people with gait disorders are also possible applications.
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The protective role of natural phytoalexin resveratrol on inflammation, fibrosis and regeneration in cholestatic liver injury.
Mol Nutr Food Res
PUBLISHED: 06-05-2011
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Liver injuries can trigger a cascade of inflammatory responses and as a result, initiate the process of hepatic regeneration and fibrogenesis. Resveratrol (RSV) has multiple health-promoting benefits. This study evaluated the potential protective effects and mechanism of RSV as related to cholestatic liver injury. RSV was given (4?mg/kg/day, i.p.) for either 3 days or 7 days after bile duct ligation (BDL) injury. RSV significantly reduced serum ALT, AST but not T-bil on Day 3. At this early stage of injury, RSV significantly reduced TNF-? and IL-6 mRNA and decreased the number of Kupffer cells (CD68(+) ) recruited in the injured liver. RSV decreased hepatic fibrosis and reduced collagen I?1 and TIMP-1 mRNA on Day 7. At the later stages of injury, RSV increased the number of Ki67(+) hepatocytes indicating that RSV promoted hepatocyte proliferation. Additionally, it resulted in decreased expression of 4-hydroxynonenal and increased expression of the hepatocyte growth factor protein and mRNA in the RSV-treated BDL group. Meanwhile, RSV reduced the mortality rate of BDL mice. In conclusion, RSV attenuated inflammation and reduced Kupffer cells activation. RSV decreased fibrosis and promoted hepatocyte regeneration, which increased the survival of BDL mice. RSV was beneficial for the treatment of cholestatic liver injury.
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Hookworm infection in a healthy adult that manifested as severe eosinphilia and diarrhea.
J Microbiol Immunol Infect
PUBLISHED: 05-23-2011
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A 54-year-old male was admitted because of having suffered from progressive watery diarrhea for 12 days. He had no history of diabetes mellitus, hypertension, heart disease, organ transplantation, or malignancy. After admission, he still complained of diarrhea despite medical treatment. The laboratory examination showed leukocytosis with eosinophilia and a stool examination by the concentration method was negative four times. When a sigmoidoscopy was performed as a part of an explorative survey, a single protruding mass consisting if a moving adult hookworm was found. The fifth stool examination by the concentration method identified hookworm ova. The patient was treated with oral mebendazole 100 mg twice a day for 3 days. The diarrhea and eosinophilia subsided after this treatment.
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Use of endoscopy with narrow-band imaging system in evaluating oral leukoplakia.
Head Neck
PUBLISHED: 05-20-2011
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The purpose of this study was to analyze the relationship between clinical features of oral leukoplakia using endoscopy with broadband white light, narrow-band imaging (NBI) illumination, and histopathology, and to discuss the clinical relevance of the NBI system.
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NSMAP: a method for spliced isoforms identification and quantification from RNA-Seq.
BMC Bioinformatics
PUBLISHED: 05-16-2011
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The development of techniques for sequencing the messenger RNA (RNA-Seq) enables it to study the biological mechanisms such as alternative splicing and gene expression regulation more deeply and accurately. Most existing methods employ RNA-Seq to quantify the expression levels of already annotated isoforms from the reference genome. However, the current reference genome is very incomplete due to the complexity of the transcriptome which hiders the comprehensive investigation of transcriptome using RNA-Seq. Novel study on isoform inference and estimation purely from RNA-Seq without annotation information is desirable.
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An immersion of Gracilaria tenuistipitata extract improves the immunity and survival of white shrimp Litopenaeus vannamei challenged with white spot syndrome virus.
Fish Shellfish Immunol.
PUBLISHED: 05-07-2011
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The innate immunity and resistance against white spot syndrome virus (WSSV) in white shrimp Litopenaeus vannamei which received the Gracilaria tenuistipitata extract were examined. Shrimp immersed in seawater containing the extract at 0 (control), 400 and 600 mg L(-1) for 3 h were challenged with WSSV at 2 × 10(4) copies shrimp(-1). Shrimp not exposed to the extract and not received WSSV challenge served as unchallenged control. The survival rate of shrimp immersed in 400 mg L(-1) or 600 mg L(-1) extract was significantly higher than that of challenged control shrimp over 24-120 h. The haemocyte count, phenoloxidase activity, respiratory burst, superoxide dismutase activity, and lysozyme activity of shrimp immersed in 600 mg L(-1) extract were significantly higher than those of unchallenged control shrimp at 6, 6, 6, 6, and 6-24 h post-challenge. In another experiment, shrimp which had received 3 h immersion of 0, 400, 600 mg L(-1) extract were challenged with WSSV. The shrimp were then received a booster (3 h immersion in the same dose of the extract), and the immune parameters were examined at 12-120 h post-challenge. The immune parameters of shrimp immersed in 600 mg L(-1) extract, and then received a booster at 9, 21, and 45 h were significantly higher than those of unchallenged control shrimp at 12-48 h post-challenge. In conclusion, shrimp which had received the extract exhibited protection against WSSV as evidenced by the higher survival rate and higher values of immune parameters. Shrimp which had received the extract and infected by WSSV showed improved immunity when they received a booster at 9, 21, and 45 h post-WSSV challenge. The extract treatment caused less decrease in PO activity, and showed better performance of lysozyme activity and antioxidant response in WSSV-infected shrimp.
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Gastrointestinal bleeding and outcomes after percutaneous coronary intervention for ST-segment elevation myocardial infarction.
Am. J. Crit. Care
PUBLISHED: 05-03-2011
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Gastrointestinal bleeding is a hemorrhagic complication after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI).
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Meta-analysis: comparison of F-18 fluorodeoxyglucose-positron emission tomography and bone scintigraphy in the detection of bone metastasis in patients with lung cancer.
Acad Radiol
PUBLISHED: 04-27-2011
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The aim of this review was to evaluate the diagnostic properties of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) or PET/computed tomography (CT) and bone scintigraphy in the detection of osseous metastases in patients with lung cancer.
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Impact of body mass index and viral load on liver histology in hepatitis B e antigen-negative chronic hepatitis B.
Clin Nutr
PUBLISHED: 04-20-2011
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The impact of overweight and obesity on chronic hepatitis B (CHB) is unclear. This study was to examine the relationship among body mass index, viral load and liver histology in HBeAg-negative CHB.
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The network properties of myelodysplastic syndromes pathogenesis revealed by an integrative systems biological method.
Mol Biosyst
PUBLISHED: 04-19-2011
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Insight into the molecular mechanism of complex diseases is an important topic in the current bio-medical research. However, different from the single-gene disorders, high heterogeneity of many of the complex diseases prevents scientists from the exact understanding of the etiology. In this study, we used Myelodysplastic Syndromes (MDSs), a heterogeneous family of clonal disorders of hematopoietic stem cells, as a general model to explore the network properties of the heterogeneity of complex diseases. First, static bioinformatics analysis suggests that despite the huge heterogeneity of MDSs, their clinical properties can be explained well by the local properties of MDS-related genes on the human interactome. Then we design a novel systems biological method to explore the pattern of genetic abnormality propagation of a real MDS cohort by integrating flowcytometry, genotyping, gene expression profiling, expression quantitative trait loci (eQTLs) mapping and pathway inference. We constructed a MDS disease gene network which suggests the network basis of the heterogeneity of MDSs. The pipeline we proposed and the implication the results suggest may be helpful in the research of other complex diseases.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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