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Find video protocols related to scientific articles indexed in Pubmed.
Efficacy and safety of puerarin injection in treatment of diabetic peripheral neuropathy: a systematic review and meta-analysis of randomized controlled trials.
J Tradit Chin Med
PUBLISHED: 09-05-2014
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To systematically evaluate the clinical efficacy and safety of puerarin injection in the treatment of diabetic peripheral neuropathy (DPN).
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Development of gold nanoparticle-sheathed glass capillary nanoelectrodes for sensitive detection of cerebral dopamine.
Biosens Bioelectron
PUBLISHED: 07-24-2014
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To develop in vivo monitoring strategies of neurotransmitters involved in brain chemistry is a challenging work for progress in understanding the roles that biomolecules play in pathology and physiology. Here we report a new type of gold nanoparticle-sheathed glass capillary nanoelectrode (Au/GCNE) for sensing cerebral dopamine. First, a size-controlled needle-type quartz capillary was pulled with a laser puller. Then, the capillary tip exterior was chemically functionalized with colloidal gold nanoparticles by the seed-mediated growth protocol. Through insulating the above tip with cathodic electrophoretic paint followed by heating to tune the exposed area of gold-nanoparticle-film, the Au/GCNE with tip apex radius ranging from ~8.9 to ~500 nm can be prepared. Scanning electron microscopy (SEM) and steady-state voltammetry were utilized to characterize the effective radius of nanoelectrodes. The results showed that the tip apex radius of Au/GCNE was mainly affected by the pre-pulled capillary tip, the modified AuNPs and the cathodic electrophoretic paint. By taking advantage of the modified AuNPs and the enhanced electrochemical performance of the nanoelectrode, a wide dynamic linear range from 2.0×10(-8) M to 5.6×10(-6) M with a low detection limit of 1.0×10(-8) M (S/N=3), as well as good selectivity for dopamine, were first achieved with the Nafion-modified Au/GCNE. In addition, the designed glass substrates of Au/GCNE were mechanically stronger and their sharp tips aided in membrane penetration during implantation in the in vivo experiment. As a result, the Nafion-modified Au/GCNE was successfully applied for amperometrically monitoring dopamine in the striatum of anesthetic rats.
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RAID: a comprehensive resource for human RNA-associated (RNA-RNA/RNA-protein) interaction.
RNA
PUBLISHED: 05-06-2014
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Transcriptomic analyses have revealed an unexpected complexity in the eukaryote transcriptome, which includes not only protein-coding transcripts but also an expanding catalog of noncoding RNAs (ncRNAs). Diverse coding and noncoding RNAs (ncRNAs) perform functions through interaction with each other in various cellular processes. In this project, we have developed RAID (http://www.rna-society.org/raid), an RNA-associated (RNA-RNA/RNA-protein) interaction database. RAID intends to provide the scientific community with all-in-one resources for efficient browsing and extraction of the RNA-associated interactions in human. This version of RAID contains more than 6100 RNA-associated interactions obtained by manually reviewing more than 2100 published papers, including 4493 RNA-RNA interactions and 1619 RNA-protein interactions. Each entry contains detailed information on an RNA-associated interaction, including RAID ID, RNA/protein symbol, RNA/protein categories, validated method, expressing tissue, literature references (Pubmed IDs), and detailed functional description. Users can query, browse, analyze, and manipulate RNA-associated (RNA-RNA/RNA-protein) interaction. RAID provides a comprehensive resource of human RNA-associated (RNA-RNA/RNA-protein) interaction network. Furthermore, this resource will help in uncovering the generic organizing principles of cellular function network.
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Qingkailing injection for the treatment of acute stroke: a systematic review and meta-analysis.
J Tradit Chin Med
PUBLISHED: 05-03-2014
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To evaluate systematically the clinical efficacy and safety of Qingkailing (QKL) injection in the treatment of acute stroke.
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Management of recurrent alveolar soft-part sarcoma of the tongue after external beam radiotherapy with iodine-125 seed brachytherapy.
Head Neck
PUBLISHED: 02-24-2014
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Alveolar soft part sarcoma (ASPS) is a rare type of soft tissue sarcoma. The infrequency of ASPS is such that it accounts for <1% of all soft tissue sarcomas and <0.1% of sarcomas concerning the head and neck, primarily those involving the orbit (48%) and tongue (25%). Traditional chemotherapy or radiotherapy of ASPS is often associated with poor outcome, even after comprehensive interventions.
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Programming a Pavlovian-like conditioning circuit in Escherichia coli.
Nat Commun
PUBLISHED: 01-18-2014
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Synthetic genetic circuits are programmed in living cells to perform predetermined cellular functions. However, designing higher-order genetic circuits for sophisticated cellular activities remains a substantial challenge. Here we program a genetic circuit that executes Pavlovian-like conditioning, an archetypical sequential-logic function, in Escherichia coli. The circuit design is first specified by the subfunctions that are necessary for the single simultaneous conditioning, and is further genetically implemented using four function modules. During this process, quantitative analysis is applied to the optimization of the modules and fine-tuning of the interconnections. Analogous to classical Pavlovian conditioning, the resultant circuit enables the cells to respond to a certain stimulus only after a conditioning process. We show that, although the conditioning is digital in single cells, a dynamically progressive conditioning process emerges at the population level. This circuit, together with its rational design strategy, is a key step towards the implementation of more sophisticated cellular computing.
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Reproducibility of magnetic resonance perfusion imaging.
PLoS ONE
PUBLISHED: 01-01-2014
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Dynamic MR biomarkers (T2*-weighted or susceptibility-based and T1-weighted or relaxivity-enhanced) have been applied to assess tumor perfusion and its response to therapies. A significant challenge in the development of reliable biomarkers is a rigorous assessment and optimization of reproducibility. The purpose of this study was to determine the measurement reproducibility of T1-weighted dynamic contrast-enhanced (DCE)-MRI and T2*-weighted dynamic susceptibility contrast (DSC)-MRI with two contrast agents (CA) of different molecular weight (MW): gadopentetate (Gd-DTPA, 0.5 kDa) and Gadomelitol (P792, 6.5 kDa). Each contrast agent was tested with eight mice that had subcutaneous MDA-MB-231 breast xenograft tumors. Each mouse was imaged with a combined DSC-DCE protocol three times within one week to achieve measures of reproducibility. DSC-MRI results were evaluated with a contrast to noise ratio (CNR) efficiency threshold. There was a clear signal drop (>95% probability threshold) in the DSC of normal tissue, while signal changes were minimal or non-existent (<95% probability threshold) in tumors. Mean within-subject coefficient of variation (wCV) of relative blood volume (rBV) in normal tissue was 11.78% for Gd-DTPA and 6.64% for P792. The intra-class correlation coefficient (ICC) of rBV in normal tissue was 0.940 for Gd-DTPA and 0.978 for P792. The inter-subject correlation coefficient was 0.092. Calculated K(trans) from DCE-MRI showed comparable reproducibility (mean wCV, 5.13% for Gd-DTPA, 8.06% for P792). ICC of K(trans) showed high intra-subject reproducibility (ICC = 0.999/0.995) and inter-subject heterogeneity (ICC = 0.774). Histograms of K(trans) distributions for three measurements had high degrees of overlap (sum of difference of the normalized histograms <0.01). These results represent homogeneous intra-subject measurement and heterogeneous inter-subject character of biological population, suggesting that perfusion MRI could be an imaging biomarker to monitor or predict response of disease.
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Protein A immunoadsorption cannot significantly remove the soluble receptor of urokinase from sera of patients with recurrent focal segmental glomerulosclerosis.
Nephrol. Dial. Transplant.
PUBLISHED: 11-13-2013
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Focal segmental glomerulosclerosis (FSGS) is a serious disease, the pathogenesis of which is unknown. Its recurrence after transplantation (Tx) and its partial remission after treatment with immunoadsorption (IA) on a protein A column indicate the existence of a circulating factor responsible for the disease that is able to bind to a protein A column. Recently, the soluble receptor of urokinase (suPAR) was described as the factor responsible for FSGS. We tested the capacity of suPAR to bind to protein A and to be eliminated by IA.
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Sequentially reweighted TV minimization for CT metal artifact reduction.
Med Phys
PUBLISHED: 07-05-2013
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Metal artifact reduction has long been an important topic in x-ray CT image reconstruction. In this work, the authors propose an iterative method that sequentially minimizes a reweighted total variation (TV) of the image and produces substantially artifact-reduced reconstructions.
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Chemopreventive effects of the juice of Vitis coignetiae Pulliat on two-stage mouse skin carcinogenesis.
Nutr Cancer
PUBLISHED: 03-28-2013
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Our study revealed the inhibitory effect of Vitis coignetiae Pulliat, known as Yamabudo in Japan, at the stages of multi-step carcinogenesis. The juice of Vitis coignetiae (Y-grape juice) was antimutagenic toward dimethylbenzo[a]anthracene (DMBA), aflatoxin B1, and benzo[a]pyrene in the Ames test. The Y-grape juice was also antigenotoxic in the micronucleus test using HepG2 cells toward DMBA and aflatoxin B1. Topical and oral administration of the Y-grape juice to mice inhibited the induction of inflammation of 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical and oral administration of the Y-grape juice significantly decreased the incidence and mean number of tumors in mice skin with the 2-stage tumorigenesis protocol. To elucidate the mechanisms underlying the antiinflammatory and antitumor promotion activity of the Y-grape juice, the effect of Y-grape juice on cyclooxygenase-2 (COX-2) activity in mouse ear treated with TPA was studied. Both topical and oral application of the Y-grape juice inhibited the TPA-induced increase in COX-2 activity. Caftaric acid, isolated and identified from the Y-grape juice, was antimutagenic toward DMBA and prevented TPA-induced inflammation in mice, suggesting caftaric acid participates in chemopreventive effect/activities of Y-grape juice.
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The Hippo pathway and human cancer.
Nat. Rev. Cancer
PUBLISHED: 03-07-2013
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The Hippo pathway controls organ size in diverse species, whereas pathway deregulation can induce tumours in model organisms and occurs in a broad range of human carcinomas, including lung, colorectal, ovarian and liver cancer. Despite this, somatic or germline mutations in Hippo pathway genes are uncommon, with only the upstream pathway gene neurofibromin 2 (NF2) recognized as a bona fide tumour suppressor gene. In this Review, we appraise the evidence for the Hippo pathway as a cancer signalling network, and discuss cancer-relevant biological functions, potential mechanisms by which Hippo pathway activity is altered in cancer and emerging therapeutic strategies.
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Fragment-based design of novel quinazolinon derivatives as human acrosin inhibitors.
Chem Biol Drug Des
PUBLISHED: 01-02-2013
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Human acrosin is a promising target for the male contraceptives. On the basis of the active site of human acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy. In vitro anti-acrosin assay revealed that all the compounds showed potent human acrosin inhibitory activities. In particular, compounds 5c and 5g are more active than the known inhibitors. Molecular docking studies revealed that the quinazolinon inhibitors interacted with human acrosin mainly through hydrogen bonding and hydrophobic interactions. The binding mode was also consistent with the structure-activity relationships. The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives.
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A reverse engineering approach to optimize experiments for the construction of biological regulatory networks.
PLoS ONE
PUBLISHED: 01-01-2013
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One of the major objectives in systems biology is to understand the relation between the topological structures and the dynamics of biological regulatory networks. In this context, various mathematical tools have been developed to deduct structures of regulatory networks from microarray expression data. In general, from a single data set, one cannot deduct the whole network structure; additional expression data are usually needed. Thus how to design a microarray expression experiment in order to get the most information is a practical problem in systems biology. Here we propose three methods, namely, maximum distance method, trajectory entropy method, and sampling method, to derive the optimal initial conditions for experiments. The performance of these methods is tested and evaluated in three well-known regulatory networks (budding yeast cell cycle, fission yeast cell cycle, and E. coli. SOS network). Based on the evaluation, we propose an efficient strategy for the design of microarray expression experiments.
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[Utilization of functional surgery in benign parotid tumor of superficial lobe].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-21-2011
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To investigate the utilization of functional surgery in benign parotid tumor of superficial lobe.
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The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway.
Dev. Cell
PUBLISHED: 05-16-2011
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The Salvador-Warts-Hippo (SWH) pathway is a complex signaling network that controls both developmental and regenerative tissue growth. Using a genetic screen in Drosophila melanogaster, we identified the sterile 20-like kinase, Tao-1, as an SWH pathway member. Tao-1 controls various biological phenomena, including microtubule dynamics, animal behavior, and brain development. Here we describe a role for Tao-1 as a regulator of epithelial tissue growth that modulates activity of the core SWH pathway kinase cassette. Tao-1 functions together with Hippo to activate Warts-mediated repression of Yorkie. Tao-1s ability to control SWH pathway activity is evolutionarily conserved because human TAO1 can suppress activity of the Yorkie ortholog, YAP. Human TAO1 controls SWH pathway activity by phosphorylating, and activating, the Hippo ortholog, MST2. Given that SWH pathway activity is subverted in many human cancers, our findings identify human TAO kinases as potential tumor suppressor genes.
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Metal artifact reduction in x-ray computed tomography (CT) by constrained optimization.
Med Phys
PUBLISHED: 04-02-2011
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The streak artifacts caused by metal implants have long been recognized as a problem that limits various applications of CT imaging. In this work, the authors propose an iterative metal artifact reduction algorithm based on constrained optimization.
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Imaging pH and metastasis.
NMR Biomed
PUBLISHED: 03-08-2011
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Metastasis is a multistep process that culminates in the spread of cells from a primary tumor to a distant site or organs. For tumor cells to be able to metastasize, they have to locally invade through basement membrane into the lymphatic and the blood vasculatures. Eventually they extravasate from the blood and colonize in the secondary organ. This process involves multiple interactions between the tumor cells and their microenvironments. The microenvironment surrounding tumors has a significant impact on tumor development and progression. A key factor in the microenvironment is an acidic pH. The extracellular pH of solid tumors is more acidic in comparison to normal tissue as a consequence of high glycolysis and poor perfusion. It plays an important role in almost all steps of metastasis. The past decades have seen development of technologies to non-invasively measure intra- and/or extracellular pH. Most successful measurements are MR-based, and sensitivity and accuracy have dramatically improved. Quantitatively imaging the distribution of acidity helps us understand the role of the tumor microenvironment in cancer progression. The present review discusses different MR methods in measuring tumor pH along with emphasizing the importance of extracelluar tumor low pH on different steps of metastasis; more specifically focusing on epithelial-to-mesenchymal transition (EMT), and anti cancer immunity.
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In vitro and in vivo study of a nanoliposomal cisplatin as a radiosensitizer.
Int J Nanomedicine
PUBLISHED: 02-21-2011
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To investigate the in vitro and in vivo radiosensitization effect of an institutionally designed nanoliposome encapsulated cisplatin (NLE-CDDP).
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Imaging the extracellular pH of tumors by MRI after injection of a single cocktail of T1 and T2 contrast agents.
NMR Biomed
PUBLISHED: 01-28-2011
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The extracellular pH (pH(e) ) of solid tumors is acidic, and there is evidence that an acidic pH(e) is related to invasiveness. Herein, we describe an MRI single-infusion method to measure pH(e) in gliomas using a cocktail of contrast agents (CAs). The cocktail contained gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (GdDOTA-4AmP) and dysprosium-1,4,7,10-tetraazacyclododecane-N,N,N,N-tetrakis(methylenephosphonic acid) (DyDOTP), whose effects on relaxation are sensitive and insensitive to pH, respectively. The Gd-CA dominated the spin-lattice relaxivity ?R(1) , whereas the Dy-CA dominated the spin-spin relaxivity ?R(2)*. The ?R(2)* effects were used to determine the pixel-wise concentration of [Dy] which, in turn, was used to calculate a value for [Gd] concentration. This value was used to convert ?R(1) values to the molar relaxivity ?r(1) and, hence, pH(e) maps. The development of the method involved in vivo calibration and measurements in a rat brain glioma model. The calibration phase consisted of determining a quantitative relationship between ?R(1) and ?R(2)* induced by the two pH-independent CAs, gadolinium-diethylenetriaminepentaacetic acid (GdDTPA) and DyDOTP, using echo planar spectroscopic imaging (EPSI) and T(1) -weighted images. The intensities and linewidths of the water peaks in EPSI images were affected by CA and were used to follow the pharmacokinetics. These data showed a linear relationship between inner- and outer-sphere relaxation rate constants that were used for CA concentration determination. Nonlinearity in the slope of the relationship was observed and ascribed to variations in vascular permeability. In the pH(e) measurement phase, GdDOTA-4AmP was infused instead of GdDTPA, and relaxivities were obtained through the combination of interleaved T(1) -weighted images (R(1) ) and EPSI for ?R(2)*. The resulting r(1) values yielded pH(e) maps with high spatial resolution.
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Anti-genotoxic activity of Vitis coignetiae Pulliat towards heterocyclic amines and isolation and identification of caftaric acid as an antimutagenic component from the juice.
Mutat. Res.
PUBLISHED: 01-27-2011
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Our study demonstrated that the formation of DNA adducts in liver, lungs, colon and kidneys of mice given a carcinogenic heterocyclic amine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in the diet significantly decreased following the administration of the juice of Vitis coignetiae, purple berries from a vine tree. The juice of V. coignetiae significantly inhibited the clastogenicity and mutagenicity of heterocyclic amines in the micronucleus assay and the Ames test, and was an effective inhibitor of the activities of phase I enzymes (cytochrome P450 1A1 and cytochrome P450 1A2) and enhancer of the activities of phase II enzymes (uridine 5-diphospho-glucuronosyltransferase and glutathione S-transferase). We investigated the purification and isolation of an active compound in the juice of V. coignetiae using antimutagenicity as a separation marker. Caftaric acid, a polyphenolic compound, was identified as a component responsible for antimutagenicity in the juice of V. coignetiae towards the carcinogenic heterocyclic amine 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). This is the first report of antimutagenicity of caftaric acid. Caftaric acid was reported as an inhibitor of the protein-protein interactions mediated by the Src-family kinases. The impact of the juice of V. coignetiae and its constituents on tumor initiation and promotion thus warrants further study.
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The influence of creative process engagement on employee creative performance and overall job performance: a curvilinear assessment.
J Appl Psychol
PUBLISHED: 08-20-2010
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Integrating theories addressing attention and activation with creativity literature, we found an inverted U-shaped relationship between creative process engagement and overall job performance among professionals in complex jobs in an information technology firm. Work experience moderated the curvilinear relationship, with low-experience employees generally exhibiting higher levels of overall job performance at low to moderate levels of creative process engagement and high-experience employees demonstrating higher overall performance at moderate to high levels of creative process engagement. Creative performance partially mediated the relationship between creative process engagement and job performance. These relationships were tested within a moderated mediation framework.
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Tumor pH and its measurement.
J. Nucl. Med.
PUBLISHED: 07-21-2010
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Studies over the last few decades have demonstrated that the intracellular pH of solid tumors is maintained within a range of 7.0-7.2, whereas the extracellular pH is acidic. A low extracellular pH may be an important factor inducing more aggressive cancer phenotypes. Research into the causes and consequences of this acidic pH of tumors is highly dependent on accurate, precise, and reproducible measurements, and these have undergone great changes in the last decade. This review focuses on the most recent advances in the in vivo measurement of tumor pH by pH-sensitive PET radiotracers, MR spectroscopy, MRI, and optical imaging.
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[Utilization of functional neck dissection for treatment of recurrent branchial cleft anomalies].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 06-04-2010
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To evaluate the utilization of functional neck dissection for treatment of recurrent branchial cleft anomalies.
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Differential requirement of Salvador-Warts-Hippo pathway members for organ size control in Drosophila melanogaster.
Development
PUBLISHED: 01-28-2010
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The Salvador-Warts-Hippo (SWH) pathway contains multiple growth-inhibitory proteins that control organ size during development by limiting activity of the Yorkie oncoprotein. Increasing evidence indicates that these growth inhibitors act in a complex network upstream of Yorkie. This complexity is emphasised by the distinct phenotypes of tissue lacking different SWH pathway genes. For example, eye tissue lacking the core SWH pathway components salvador, warts or hippo is highly overgrown and resistant to developmental apoptosis, whereas tissue lacking fat or expanded is not. Here we explore the relative contribution of SWH pathway proteins to organ size control by determining their temporal activity profile throughout Drosophila melanogaster eye development. We show that eye tissue lacking fat, expanded or discs overgrown displays elevated Yorkie activity during the larval growth phase of development, but not in the pupal eye when apoptosis ensues. Fat and Expanded do possess Yorkie-repressive activity in the pupal eye, but loss of fat or expanded at this stage of development can be compensated for by Merlin. Fat appears to repress Yorkie independently of Dachs in the pupal eye, which would contrast with the mode of action of Fat during larval development. Fat is more likely to restrict Yorkie activity in the pupal eye together with Expanded, given that pupal eye tissue lacking both these genes resembles that of tissue lacking either gene. This study highlights the complexity employed by different SWH pathway proteins to control organ size at different stages of development.
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Transcriptional output of the Salvador/warts/hippo pathway is controlled in distinct fashions in Drosophila melanogaster and mammalian cell lines.
Cancer Res.
PUBLISHED: 07-07-2009
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The Salvador/Warts/Hippo (SWH) pathway is an important modulator of organ size, and deregulation of pathway activity can lead to cancer. Several SWH pathway components are mutated or expressed at altered levels in different human tumors including NF2, LATS1, LATS2, SAV1, and YAP. The SWH pathway regulates tissue growth by restricting the activity of the transcriptional coactivator protein known as Yorkie (Yki) in Drosophila melanogaster and Yes-associated protein (YAP) in mammals. Yki/YAP drives tissue growth in partnership with the Scalloped (Sd)/TEAD1-4 transcription factors. Yki/YAP also possesses two WW domains, which contact several proteins that have been suggested to either promote or inhibit the ability of Yki to induce transcription. To investigate the regulatory role of the Yki/YAP WW domains, we analyzed the functional consequence of mutating these domains. WW domain mutant YAP promoted transformation and migration of breast epithelial cells with increased potency, suggesting that WW domains mediate the inhibitory regulation of YAP in these cells. By contrast, the WW domains were required for YAP to promote NIH-3T3 cell transformation and for the ability of Yki to drive tissue growth in D. melanogaster and optimally activate Sd. This shows that Yki/YAP WW domains have distinct regulatory roles in different cell types and implies the existence of proteins that promote tissue growth in collaboration with Yki and Sd.
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Identification of a topological characteristic responsible for the biological robustness of regulatory networks.
PLoS Comput. Biol.
PUBLISHED: 06-19-2009
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Attribution of biological robustness to the specific structural properties of a regulatory network is an important yet unsolved problem in systems biology. It is widely believed that the topological characteristics of a biological control network largely determine its dynamic behavior, yet the actual mechanism is still poorly understood. Here, we define a novel structural feature of biological networks, termed regulation entropy, to quantitatively assess the influence of network topology on the robustness of the systems. Using the cell-cycle control networks of the budding yeast (Saccharomyces cerevisiae) and the fission yeast (Schizosaccharomyces pombe) as examples, we first demonstrate the correlation of this quantity with the dynamic stability of biological control networks, and then we establish a significant association between this quantity and the structural stability of the networks. And we further substantiate the generality of this approach with a broad spectrum of biological and random networks. We conclude that the regulation entropy is an effective order parameter in evaluating the robustness of biological control networks. Our work suggests a novel connection between the topological feature and the dynamic property of biological regulatory networks.
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[Operation pathways for sphenoidal sinus by nasal endoscope and treatments for correlated diseases beyond scope of sphenoidal sinus].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 02-25-2009
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We probe more direct operation pathways in sphenoidal sinus and saddle area, and take proper measures for correlated diseases which surpass scope of sphenoidal sinus by combining image data, which could prevent serious complication.
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Determination of spontaneous mutation frequencies in measles virus under nonselective conditions.
J. Virol.
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There is a paradox between the remarkable genetic stability of measles virus (MV) in the field and the high mutation rates implied by the frequency of the appearance of monoclonal antibody escape mutants generated when the virus is pressured to revert in vitro (S. J. Schrag, P. A. Rota, and W. J. Bellini, J. Virol. 73:51-54, 1999). We established a highly sensitive assay to determine frequencies of various categories of mutations in large populations of wild-type and laboratory-adapted MVs using recombinant viruses containing an additional transcription unit (ATU) encoding enhanced green fluorescent protein (EGFP). Single and double mutations were made in the fluorophore of EGFP to ablate fluorescence. The frequencies of reversion mutants in the population were determined by measuring the appearance of fluorescence indicating a revertant virus. This allows mutation rates to be measured under nonselective conditions, as phenotypic reversion to fluorescence requires only either a single- or a double-nucleotide change and amino acid substitution, which does not affect the length of the nonessential reporter protein expressed from the ATU. Mutation rates in MV are the same for wild-type and laboratory-adapted viruses, and they are an order of magnitude lower than the previous measurement assessed under selective conditions. The actual mutation rate for MV is approximately 1.8 × 10(-6) per base per replication event.
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Nostril-specific olfactory modulation of visual perception in binocular rivalry.
J. Neurosci.
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It is known that olfaction and vision can work in tandem to represent object identities. What is yet unclear is the stage of the sensory processing hierarchy at which the two types of inputs converge. Here we study this issue through a well established visual phenomenon termed binocular rivalry. We show that smelling an odor from one nostril significantly enhances the dominance time of the congruent visual image in the contralateral visual field, relative to that in the ipsilateral visual field. Moreover, such lateralization-based enhancement extends to category selective regions so that when two images of words and human body, respectively, are engaged in rivalry in the central visual field, smelling natural human body odor from the right nostril increases the dominance time of the body image compared with smelling it from the left nostril. Semantic congruency alone failed to produce this effect in a similar setting. These results, taking advantage of the anatomical and functional lateralizations in the olfactory and visual systems, highlight the functional dissociation of the two nostrils and provide strong evidence for an object-based early convergence of olfactory and visual inputs in sensory representations.
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Yap controls stem/progenitor cell proliferation in the mouse postnatal epidermis.
J. Invest. Dermatol.
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Tissue renewal is an ongoing process in the epithelium of the skin. We have begun to examine the genetic mechanisms that control stem/progenitor cell activation in the postnatal epidermis. The conserved Hippo pathway regulates stem cell turnover in arthropods through to vertebrates. Here we show that its downstream effector, yes-associated protein (YAP), is active in the stem/progenitor cells of the postnatal epidermis. Overexpression of a C-terminally truncated YAP mutant in the basal epidermis of transgenic mice caused marked expansion of epidermal stem/progenitor cell populations. Our data suggest that the C-terminus of YAP controls the balance between stem/progenitor cell proliferation and differentiation in the postnatal interfollicular epidermis. We conclude that YAP functions as a molecular switch of stem/progenitor cell activation in the epidermis. Moreover, our results highlight YAP as a possible therapeutic target for diseases such as skin cancer, psoriasis, and epidermolysis bullosa.
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Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo.
Cancer Lett.
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The multikinase-inhibition action of sorafenib provides strong rationales for its combination use with radiotherapy. We investigated the in vitro and in vivo effect of sorafenib combined with irradiation on hepatocellular carcinoma (HCC). Sorafenib enhanced radiosensitivity of human HCC cell lines in a schedule-dependent manner. Sorafenib selectively inhibited radiation-induced activation of vascular endothelial growth factor receptor-2 (VEGFR2) and downstream extracellular signal-regulated kinase (ERK) pathway, induced DNA damage and suppressed DNA repair capacity, decreased radiation-activated NF-?B and increased radiation-induced apoptosis. In xenograft experiments, combination treatment produced marked tumor growth delay in both concurrent and sequential schedules. These results suggest that sorafenib could potentiate irradiation effect in HCC, which warrants further investigation for its potential clinical applications.
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Homeodomain-interacting protein kinase regulates Hippo pathway-dependent tissue growth.
Curr. Biol.
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The Salvador-Warts-Hippo (SWH) pathway is an evolutionarily conserved regulator of tissue growth that is deregulated in human cancer. Upstream SWH pathway components convey signals from neighboring cells via a core kinase cassette to the transcription coactivator Yorkie (Yki). Yki controls tissue growth by modulating activity of transcription factors including Scalloped (Sd). To date, five SWH pathway kinases have been identified, but large-scale phosphoproteome studies suggest that unidentified SWH pathway kinases exist. To identify such kinases, we performed an RNA interference screen and isolated homeodomain-interacting protein kinase (Hipk). Unlike previously identified SWH pathway kinases, Hipk is unique in its ability to promote, rather than repress, Yki activity and does so in parallel to the Yki-repressive kinase, Warts (Wts). Hipk is required for basal Yki activity and is likely to regulate Yki function by promoting its accumulation in the nucleus. Like many SWH pathway proteins, Hipks function is evolutionarily conserved as its closest human homolog, HIPK2, promotes activity of the Yki ortholog YAP in a kinase-dependent fashion. Further, HIPK2 promotes YAP abundance, suggesting that the mechanism by which HIPK2 regulates YAP has diverged in mammals.
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Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway.
PLoS ONE
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The Salvador-Warts-Hippo (SWH) pathway is an important regulator of tissue growth that is frequently subverted in human cancer. The key oncoprotein of the SWH pathway is the transcriptional co-activator, Yes-associated protein (YAP). YAP promotes tissue growth and transformation of cultured cells by interacting with transcriptional regulatory proteins via its WW domains, or, in the case of the TEAD1-4 transcription factors, an N-terminal binding domain. YAP possesses a putative transactivation domain in its C-terminus that is necessary to stimulate transcription factors in vitro, but its requirement for YAP function has not been investigated in detail. Interestingly, whilst the WW domains and TEAD-binding domain are highly conserved in the Drosophila melanogaster YAP orthologue, Yorkie, the majority of the C-terminal region of YAP is not present in Yorkie. To investigate this apparent conundrum, we assessed the functional roles of the YAP and Yorkie C-termini. We found that these regions were not required for Yorkies ability to drive tissue growth in vivo, or YAPs ability to promote anchorage-independent growth or resistance to contact inhibition. However, the YAP transactivation domain was required for YAPs ability to induce cell migration and invasion. Moreover, a role for the YAP transactivation domain in cell transformation was uncovered when the YAP WW domains were mutated together with the transactivation domain. This shows that YAP can promote cell transformation in a flexible manner, presumably by contacting transcriptional regulatory proteins either via its WW domains or its transactivation domain.
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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.