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Find video protocols related to scientific articles indexed in Pubmed.
Notch1 mutations are drivers of oral tumorigenesis.
Cancer Prev Res (Phila)
PUBLISHED: 11-20-2014
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Disruption of NOTCH1 signaling was recently discovered in head and neck cancer. This study aims to evaluate NOTCH1 alterations in the progression of oral squamous cell carcinoma (OSCC) and compare the occurrence of these mutations in Chinese and Caucasian populations. We used a high-throughput-PCR-based enrichment technology and next generation sequencing (NGS) to sequence NOTCH1 in 144 samples collected in China. Forty nine samples were normal oral mucosa from patients undergoing oral surgery, 45 were oral leukoplakia biopsies and 50 were chemoradiation naïve OSCC samples with 22 paired-normal tissues from the adjacent unaffected areas. NOTCH1 mutations were found in 54% of primary OSCC and 60% of pre-malignant lesions. Importantly, almost 60% of leukoplakia patients with mutated NOTCH1 carried mutations that were also identified in OSCC, indicating an important role of these clonal events in the progression of early neoplasms. We then compared all known NOTCH1 mutations identified in Chinese OSCC patients with those reported in Caucasians to date. Although we found obvious overlaps in critical regulatory NOTCH1 domains alterations and identified specific mutations shared by both groups, possible gain-of-function mutations were predominantly seen in Chinese population. Our findings demonstrate that pre-malignant lesions display NOTCH1 mutations at an early stage and are thus bona fide drivers of OSCC progression. Moreover, our results reveal that NOTCH1 promotes distinct tumorigenic mechanisms in patients from different ethnical populations.
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Brownian Motion of Arbitrarily Shaped Particles in Two Dimensions.
Langmuir
PUBLISHED: 10-31-2014
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We implement microfabricated boomerang particles with unequal arm lengths as a model for nonsymmetric particles and study their Brownian motion in a quasi-two-dimensional geometry by using high-precision single-particle motion tracking. We show that because of the coupling between translation and rotation, the mean squared displacements of a single asymmetric boomerang particle exhibit a nonlinear crossover from short-time faster to long-time slower diffusion, and the mean displacements for fixed initial orientation are nonzero and saturate out at long times. The measured anisotropic diffusion coefficients versus the tracking point position indicate that there exists one unique point, i.e., the center of hydrodynamic stress (CoH), at which all coupled diffusion coefficients vanish. This implies that in contrast to motion in three dimensions where the CoH exists only for high-symmetry particles, the CoH always exists for Brownian motion in two dimensions. We develop an analytical model based on Langevin theory to explain the experimental results and show that among the six anisotropic diffusion coefficients only five are independent because the translation-translation coupling originates from the translation-rotation coupling. Finally, we classify the behavior of two-dimensional Brownian motion of arbitrarily shaped particles into four groups based on the particle shape symmetry group and discussed potential applications of the CoH in simplifying understanding of the circular motions of microswimmers.
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Time-resolved in situ detection of CO in a shock tube using cavity-enhanced absorption spectroscopy with a quantum-cascade laser near 4.6µm.
Opt Express
PUBLISHED: 10-17-2014
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Cavity-enhanced absorption spectroscopy (CEAS) using a mid-infrared DFB quantum-cascade laser is reported for sensitive time-resolved (10 ?s) in situ CO measurements in a shock tube. Off-axis alignment and fast scanning of the laser wavelength were used to minimize coupling noise in a low-finesse cavity. An absorption gain factor of 91 was demonstrated, which enabled sub-ppm detection sensitivity for gas temperatures of 1000-2100K in a 15 cm diameter shock tube. This substantial improvement in detection sensitivity compared to conventional single-pass absorption measurements, shows great potential for the study of reaction pathways of high-temperature combustion kinetics mechanisms in shock tubes.
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ROCK-dependent ATP5D modulation contributes to the protection of notoginsenoside NR1 against ischemia/reperfusion-induced myocardial injury.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 10-12-2014
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Cardiac ischemia-reperfusion (I/R) injury remains a challenge for clinicians, which initiates with energy metabolism disorder. The present study was designed to investigate the protective effect of Notoginsenoside R1 (NR1) on I/R-induced cardiac injury and underlying mechanism. Male Sprague-Dawley rats were subjected to 30 min occlusion of left coronary anterior descending artery followed by reperfusion with or without NR1 pretreatment (5 mg/kg/hour). In vitro, H9c2 cells were cultured in oxygen and glucose deprivation/reoxygenation (OGD/R) condition after NR1 (0.1 mM), Rho kinase (ROCK) inhibitor Y-27632 (10 ?M) or RhoA/ROCK activator U-46619 (10 nM) administration. Myocardial infarct size, myocardial histology and cardiac function were evaluated. Myo?bril and mitochondria morphology were observed by transmission electron microscopy. F-actin and apoptosis were determined by immuno?uorescence and TUNEL staining. ATP and AMP content were assessed by ELISA. P-AMPK, ATP synthase subunits, apoptosis-related molecules and the level and activity of ROCK were determined by Western blotting. We found NR1 pretreatment ameliorated myocardial infarction, histological injury and cardiac function induced by I/R. Furthermore, similar to the effect of Y-27632, NR1 improved H9c2 cell viability, maintained actin skeleton and mitochondria morphology, and apoptosis induced by OGD/R. Importantly, NR1 prevented energy abnormity, inhibited the expression and activation of ROCK, restored the expression of ATP5D both in vivo and in vitro. Whereas, U-46619 suppressed the effect of NR1. These results prove NR1 as an agent able to prevent I/R-induced energy metabolism disorder via inhibiting ROCK and enhancing ATP5D, which at least partially contributes to its protection against cardiac I/R injury.
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Experimental demonstration of the einstein-podolsky-rosen steering game based on the all-versus-nothing proof.
Phys. Rev. Lett.
PUBLISHED: 09-30-2014
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Einstein-Podolsky-Rosen (EPR) steering, a generalization of the original concept of "steering" proposed by Schrödinger, describes the ability of one system to nonlocally affect another system's states through local measurements. Some experimental efforts to test EPR steering in terms of inequalities have been made, which usually require many measurement settings. Analogy to the "all-versus-nothing" (AVN) proof of Bell's theorem without inequalities, testing steerability without inequalities would be more strong and require less resources. Moreover, the practical meaning of steering implies that it should also be possible to store the state information on the side to be steered, a result that has not yet been experimentally demonstrated. Using a recent AVN criterion for two-qubit entangled states, we experimentally implement a practical steering game using quantum memory. Furthermore, we develop a theoretical method to deal with the noise and finite measurement statistics within the AVN framework and apply it to analyze the experimental data. Our results clearly show the facilitation of the AVN criterion for testing steerability and provide a particularly strong perspective for understanding EPR steering.
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[Analysis of pathogenic spectrum and risk factors in 165 non-transplant patients with invasive fungal disease].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 09-30-2014
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To describe the clinical characteristics of and risk factors for invasive fungal disease, and therefore to improve the early diagnosis and treatment of fungal infections.
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Prevalence and risk factors of abnormal left ventricular geometrical patterns in untreated hypertensive patients.
BMC Cardiovasc Disord
PUBLISHED: 09-29-2014
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The various prevalence of LVH and abnormal LV geometry have been reported in different populations. So far, only a few reports are available on the prevalence of LV geometric patterns in a large Chinese untreated hypertensive population.
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Structural evolution of NiAu nanoparticles under ambient conditions directly revealed by atom-resolved imaging combined with DFT simulation.
Nanoscale
PUBLISHED: 09-19-2014
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From an economic point of view, the structural stability of noble-transition bimetallic catalysts is as significant as their well-studied catalytic efficiency. The structural evolution and corresponding dynamics of NiAu bimetallic nanoparticles under ambient conditions are investigated using in situ Cs-corrected STEM and DFT calculations. During oxidization, the Au component promotes dissociation of oxygen and initiates Ni oxidization, which simultaneously drives the migration of Au atoms, thus yielding multi-shell structures (denoted by Ni@Au@NiO). The subsequent hydrogen reduction induces surface reconstruction, forming fcc-NiAu clusters. After several cycles of catalyzing CO oxidization, both inverse Au segregation and Ni recrystallization occur, which are ascribed to exothermic excitation. The results of this study can help researchers understand the evolutionary behaviors of the bimetallic nanoparticles under ambient conditions as well as optimize the structural design of bimetallic catalysts.
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Efficient imidation of C(sp3)-H bonds adjacent to oxygen atoms of aryl ethers under metal-free conditions.
Chem. Commun. (Camb.)
PUBLISHED: 09-13-2014
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An intermolecular oxidative C-N formation reaction of aryl ethers with pharmacological saccharins was realized under metal-free conditions for the first time. The understanding of the intrinsic characteristics between C(sp(3))-H and C(sp(2))-O bonds of aryl ethers and their potential for application might promote more research interest in this area.
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Thermally sensitive self-assembly of glucose-functionalized tetrachloro-perylene bisimides: from twisted ribbons to microplates.
Langmuir
PUBLISHED: 09-09-2014
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Chiral supramolecular structures are becoming increasingly attractive for their specific molecular arrangements, exceptional properties, and promising applications in chiral sensing and separation. However, constructing responsive chiral supramolecular structures remains a great challenge. Here, glucose-functionalized tetrachloro-perylene bisimides (GTPBIs) with thermally sensitive self-assembly behaviors are designed and synthesized. In a methanol/water mixture, GTPBIs self-assembled into twisted ribbons and microplates at 4 and 25 °C, respectively. Furthermore, the ribbon structure was metastable and could transform into microplates when the temperature was increased from 4 to 25 °C. Transmission electron microscopy (TEM) was used to track the evolution of morphology and study the assembly mechanisms of correponding nanostructures at different time intervals. The supramolecular structures were characterized with various techniques, including circular dichroism, TEM, scanning electron microscopy, atomic force microscopy, ultraviolet-visible absorption, and fluorescence spectra. This study provides insight into controlling molecular parameters and assembly conditions to construct chiral supramolecular structures.
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Regioselective C?H Imidation of Five-Membered Heterocyclic Compounds through a Metal Catalytic or Organocatalytic Approach.
Chem Asian J
PUBLISHED: 09-08-2014
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An efficient method for the synthesis of 2-amino and ?-amino five-membered heterocyclic derivatives that are closely related to a variety of biologically active natural products is described. Regioselectivity was achieved through a metal catalytic or organocatalytic approach. Preliminary studies on the reaction mechanism suggest a radical imidation pathway; however, further studies are needed to verify the mechanism.
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[Comparison of clinical characteristics and survival on patients with idiopathic pulmonary arterial hypertension and familial pulmonary arterial hypertension during conventional therapy era and targeted therapy era].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 08-29-2014
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To compare the clinical characteristics and survival on Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) and familiar pulmonary arterial hypertension (FPAH) during conventional therapy era and targeted therapy era.
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Differential degradation for small heat shock proteins IbpA and IbpB is synchronized in Escherichia coli: implications for their functional cooperation in substrate refolding.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-28-2014
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Small heat shock proteins (sHSPs), as a conserved family of ATP-independent molecular chaperones, are known to bind non-native substrate proteins and facilitate the substrate refolding in cooperation with ATP-dependent chaperones (e.g., DnaK and ClpB). However, how different sHSPs function in coordination is poorly understood. Here we report that IbpA and IbpB, the two sHSPs of Escherichia coli, are coordinated by synchronizing their differential in vivo degradation. Whereas the individually expressed IbpA and IbpB are respectively degraded slowly and rapidly in cells cultured under both heat shock and normal conditions, their simultaneous expression leads to a synchronized degradation at a moderate rate. Apparently, such synchronization is linked to their hetero-oligomerization and cooperation in binding substrate proteins. In addition, truncation of the flexible N- and C-terminal tails dramatically suppresses the IbpB degradation, and somehow accelerates the IbpA degradation. In view of these in vivo data, we propose that the synchronized degradation for IbpA and IbpB are crucial for their synergistic promoting effect on DnaK/ClpB-mediated substrate refolding, conceivably via the formation of IbpA-IbpB-substrate complexes. This scenario may be common for different sHSPs that interact with each other in cells.
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Peroxides as "switches" of dialkyl H-phosphonate: two mild and metal-free methods for preparation of 2-acylbenzothiazoles and dialkyl benzothiazol-2-ylphosphonates.
J. Org. Chem.
PUBLISHED: 08-25-2014
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Two mild and metal-free methods for the preparation of two kinds of important benzothiazole derivatives, 2-acylbenzothiazoles and dialkyl benzothiazol-2-ylphosphonates, respectively, were developed. The dialkyl H-phosphonate (RO)2P(O)H exists in equilibrium with its tautomer dialkyl phosphite (RO)2POH. TBHP triggered ?-carbon-centered phosphite radical formation, whereas DTBP triggered phosphorus-centered phosphonate radical formation. The two types of radicals led respectively to two different reaction processes, the direct C2-acylation of benzothiazoles and C2-phosphonation of benzothiazoles.
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Predicting disease associations via biological network analysis.
BMC Bioinformatics
PUBLISHED: 08-19-2014
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Understanding the relationship between diseases based on the underlying biological mechanisms is one of the greatest challenges in modern biology and medicine. Exploring disease-disease associations by using system-level biological data is expected to improve our current knowledge of disease relationships, which may lead to further improvements in disease diagnosis, prognosis and treatment.
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The integrated disease network.
Integr Biol (Camb)
PUBLISHED: 08-19-2014
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The growing body of transcriptomic, proteomic, metabolomic and genomic data generated from disease states provides a great opportunity to improve our current understanding of the molecular mechanisms driving diseases and shared between diseases. The use of both clinical and molecular phenotypes will lead to better disease understanding and classification. In this study, we set out to gain novel insights into diseases and their relationships by utilising knowledge gained from system-level molecular data. We integrated different types of biological data including genome-wide association studies data, disease-chemical associations, biological pathways and Gene Ontology annotations into an Integrated Disease Network (IDN), a heterogeneous network where nodes are bio-entities and edges between nodes represent their associations. We also introduced a novel disease similarity measure to infer disease-disease associations from the IDN. Our predicted associations were systemically evaluated against the Medical Subject Heading classification and a statistical measure of disease co-occurrence in PubMed. The strong correlation between our predictions and co-occurrence associations indicated the ability of our approach to recover known disease associations. Furthermore, we presented a case study of Crohn's disease. We demonstrated that our approach not only identified well-established connections between Crohn's disease and other diseases, but also revealed new, interesting connections consistent with emerging literature. Our approach also enabled ready access to the knowledge supporting these new connections, making this a powerful approach for exploring connections between diseases.
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Silk fibroin/collagen and silk fibroin/chitosan blended three-dimensional scaffolds for tissue engineering.
Eur J Orthop Surg Traumatol
PUBLISHED: 08-14-2014
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In this study, the silk fibroin blended constructs were produced, scaffold performances of different kinds of scaffold were analyzed, and the better type for tissue engineering was optimized.
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Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy.
Eur. J. Heart Fail.
PUBLISHED: 07-31-2014
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Although genetic testing has been recommended in patients with hypertrophic cardiomyopathy (HCM) in current clinical practice, its utility in prognostic prediction remains to be ascertained. We assessed the dosage effect of rare variants in sarcomere genes on the long-term outcomes of HCM.
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Up-regulation of hexokinase1 in the right ventricle of monocrotaline induced pulmonary hypertension.
Respir. Res.
PUBLISHED: 07-23-2014
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Pulmonary arterial hypertension (PAH) is a proliferative arteriopathy associated with a glycolytic shift during heart metabolism. An increase in glycolytic metabolism can be detected in the right ventricle during PAH. Expression levels of glycolysis genes in the right ventricle during glycolysis that occur in monocrotaline (MCT)-induced pulmonary hypertension (PH) remain unknown.
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[Pulmonary arterial hypertension after operation for congenital heart disease: analysis of baseline clinical characteristics of 122 Chinese patients].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 07-22-2014
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To explore the baseline clinical characteristics of patients with pulmonary arterial hypertension after operation for congenital heart disease (AO-CHD-PAH) in China.
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Treatment of chronic graft-versus-host disease with bortezomib.
Blood
PUBLISHED: 07-09-2014
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Chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) has emerged as a predominant complication following HSCT and has a distinct etiology. We and others have previously demonstrated that bortezomib, a proteasome inhibitor, can prevent but not treat acute GVHD in mice. To assess the effects of bortezomib on cGVHD, a mouse minor histocompatibility antigen-mismatched strain combination was used to mimic clinical cGVHD sclerodermatous pathogenesis and phenotype. Treatment of ongoing cGVHD with bortezomib ameliorated cutaneous lesions, which were also associated with a reduction in total numbers of germinal center B cells and lower B-cell activating factor gene expression levels in cutaneous tissues. Importantly, lymphoma-bearing mice receiving allogeneic HSCT with bortezomib preserved graft-versus-tumor (GVT) effects. Based on these animal studies, we initiated an intrapatient dose escalation clinical trial in patients with extensive steroid-intolerant, dependent, or resistant cGVHD. Marked clinical improvement was observed in patients, which was also associated with reductions of peripheral B cells and minimal toxicity. These results indicate that bortezomib can be of significant use in the treatment of cGVHD and may also allow for maintenance of GVT. This trial was registered at www.clinicaltrials.gov as #NCT01672229.
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Clinical features and therapeutic strategies of obstructive azoospermia in patients treated by bilateral inguinal hernia repair in childhood.
Asian J. Androl.
PUBLISHED: 07-05-2014
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Childhood inguinal herniorrhaphy is one common cause of seminal tract obstruction. Vasovasostomy (VV) can reconstruct seminal deferens and result in appearance of sperm and natural pregnancy in some patients. Secondary epididymal obstruction caused by a relatively long-term vasal obstruction is a common cause of lower patency compared with VV due to vasectomy in adults. From July 2007 to June 2012, a total of 62 patients, with history of childhood inguinal herniorrhaphy and diagnosed as obstructive azoospermia were treated in our center. The overall patency rate and natural pregnancy rate were 56.5% (35/62) and 25.8% (16/62), respectively. 48.4% (30/62) of the patients underwent bilateral VV in the inguinal region, with a patency rate of 76.7% (23/30) and a natural pregnancy rate of 36.7% (11/30), respectively. 30.6% (19/62) of the patients underwent bilateral VV and unilateral or bilateral vasoepididymostomies due to ipsilateral epididymal obstruction with the patency and natural pregnancy rate decreasing to 63.2% (12/19) and 26.3% (5/19). 21.0% (13/62) of the patients merely underwent vasal exploration without reconstruction due to failure to find distal vasal stump, etc. Our study indicate that microsurgical reanastomosis is an effective treatment for some patients with seminal tract obstruction caused by childhood inguinal herniorrhaphy.
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Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure.
Mol Metab
PUBLISHED: 07-01-2014
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We recently reported that local overexpression of VEGF-A in white adipose tissue (WAT) protects against diet-induced obesity and metabolic dysfunction. The observation that VEGF-A induces a "brown adipose tissue (BAT)-like" phenotype in WAT prompted us to further explore the direct function of VEGF-A in BAT. We utilized a doxycycline (Dox)-inducible, brown adipocyte-specific VEGF-A transgenic overexpression model to assess direct effects of VEGF-A in BAT in vivo. We observed that BAT-specific VEGF-A expression increases vascularization and up-regulates expression of both UCP1 and PGC-1? in BAT. As a result, the transgenic mice show increased thermogenesis during chronic cold exposure. In diet-induced obese mice, introducing VEGF-A locally in BAT rescues capillary rarefaction, ameliorates brown adipocyte dysfunction, and improves deleterious effects on glucose and lipid metabolism caused by a high-fat diet challenge. These results demonstrate a direct positive role of VEGF-A in the activation and expansion of BAT.
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Size-dependent property and cell labeling of semiconducting polymer dots.
ACS Appl Mater Interfaces
PUBLISHED: 06-25-2014
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Semiconducting polymer dots (Pdots) represent a new class of fluorescent nanoparticles for biological applications. In this study, we investigated their size-dependent fluorescence and cellular labeling properties. We demonstrate that the polymer conformation in solution phase largely affects the polymer folding and packing during the nanoparticle preparation process, resulting in solution-phase control over the fluorescence properties of semiconducting polymer nanoparticles. The resulting Pdots exhibit apparent size dependent absorption and emission, a characteristic feature of different chain packing behaviors due to the preparation conditions. Single-particle fluorescence imaging was employed to perform a side-by-side comparison on the Pdot brightness, indicating a quadratic dependence of single-particle brightness on particle size. Upon introducing a positively charged dye Nile blue, all the three type of Pdots were quenched very efficiently (Ksv > 1 × 10(7) M(-1)) in an applied quenching process at low dye concentrations, but exhibit apparent difference in quenching efficiency with increasing dye concentration. Furthermore, Pdots of different sizes were used for cell uptake and cellular labeling involving biotin-streptavidin interactions. Fluorescence imaging together with flow cytometry studies clearly showed size dependent labeling brightness. Small-sized Pdots appear to be more effective for immunolabeling of cell surface, whereas medium-sized Pdots exhibit the highest uptake efficiency. This study provides a concrete guidance for selecting appropriate particle size for biological imaging and sensing applications.
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Relationship of meeting physical activity guidelines with quality-adjusted life-years.
Semin. Arthritis Rheum.
PUBLISHED: 06-15-2014
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The quality-adjusted life-year (QALY) is a standard outcome measure used in cost-effectiveness analyses. This study investigates whether attainment of federal physical activity guidelines is associated with higher QALY estimates among adults with or at an increased risk for knee osteoarthritis.
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Cell-based therapy for acute and chronic liver failures: distinct diseases, different choices.
Sci Rep
PUBLISHED: 06-10-2014
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Cell-based therapies (CBTs) are considered the effective approaches to treat liver failure. However, which cell type is the most suitable source of CBTs for acute liver failure (ALF) or chronic liver failure (CLF) remains unclear. To investigate this, mature hepatocytes in adult liver (adult HCs), fetal liver cells (FLCs), induced hepatic stem cells (iHepSCs) and bone marrow derived mesenchymal stromal cells (BMSCs) were used to CBTs for ConA-induced ALF and Fah-deficient induced CLF in mice. The results showed that only BMSCs remitted liver damage and rescued ALF in ConA-treated mice. In this process, BMSCs inhibited ConA-induced inflammatory response by decreasing the mRNA expressions of TNF-?, IFN-? and FasL and increasing IL-10 mRNA expression. However, in the CLF model, not BMSCs but adult HCs transplantation lessened liver injury, recovered liver function and rescued the life of Fah-/- mice after NTBC withdrawal. Further study showed that adult HCs offered more effective liver regeneration compared to other cells in Fah-/- mice without NTBC. These results demonstrated that BMSCs and adult HCs are the optimal sources of CBTs for ConA-induced ALF and Fah-deficient induced CLF in mice, respectively. This finding deepens our understanding about how to select a proper CBT for different liver failure.
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Isolation, plant colonization potential, and phenanthrene degradation performance of the endophytic bacterium Pseudomonas sp. Ph6-gfp.
Sci Rep
PUBLISHED: 06-10-2014
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This investigation provides a novel method of endophyte-aided removal of polycyclic aromatic hydrocarbons (PAHs) from plant bodies. A phenanthrene-degrading endophytic bacterium Pseudomonas sp. Ph6 was isolated from clover (Trifolium pratense L.) grown in a PAH-contaminated site. After being marked with the GFP gene, the colonization and distribution of strain Ph6-gfp was directly visualized in plant roots, stems, and leaves for the first time. After ryegrass (Lolium multiflorum Lam.) roots inoculation, strain Ph6-gfp actively and internally colonized plant roots and transferred vertically to the shoots. Ph6-gfp had a natural capacity to cope with phenanthrene in vitro and in planta. Ph6-gfp degraded 81.1% of phenanthrene (50 mg · L(-1)) in a culture solution within 15 days. The inoculation of plants with Ph6-gfp reduced the risks associated with plant phenanthrene contamination based on observations of decreased concentration, accumulation, and translocation factors of phenanthrene in ryegrass. Our results will have important ramifications in the assessment of the environmental risks of PAHs and in finding ways to circumvent plant PAH contamination.
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Aberrant expression and potential therapeutic target of lysophosphatidic acid receptor 3 in triple-negative breast cancers.
Clin. Exp. Med.
PUBLISHED: 06-09-2014
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Triple receptor-negative breast cancers (TNBCs) generally have poor prognoses because of the loss of therapeutic targets. As lysophosphatidic acid (LPA) receptor signaling has been shown to affect breast cancer initiation and progression, we try to evaluate the potential roles of LPA receptors in TNBCs. We examined mRNA and protein expressions of LPA receptors 1-3, using quantitative real-time PCR and immunohistochemical analyses in normal (n = 37), benign disease (n = 55), and breast cancer tissues (n = 82). Carcinomas expressed higher levels of LPA2 and LPA3 mRNAs (0.17 ± 0.070 and 0.05 ± 0.023, respectively) than did normal breast tissue (0.13 ± 0.072 and 0.02 ± 0.002, respectively). Enhanced immunohistochemical staining for LPA2 and LPA3 protein was also consistently observed in carcinomas. The LPA3 overexpression was associated with lymph node metastases, and absence of estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression. TNBC tissues and cell lines showed the highest LPA3 expression compared with luminal-type A and B breast cancers. Suppression of LPA3 by shRNA did not influence cell growth in breast cancer cells. However, the migration and invasion of TNBC cells were significantly inhibited by LPA3-shRNA or inhibitor, which had no or less effect on normal and non-TNBC breast cells. In conclusion, our data indicated that the expression of LPA receptor 3 was increased in human TNBCs and is associated with tumor metastatic ability, and this implies that LPA3 is a potential therapeutic target for the treatment of TNBCs.
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ER? upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue.
Mol Metab
PUBLISHED: 06-07-2014
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Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor ? (ER?) have the opposite effect. Here we identify an Estrogen Response Element (ERE) in the promoter of Phd3, which is a negative regulatory enzyme of HIF-1, and we demonstrate HIF-1? is ubiquitinated following 17-? estradiol (E2)/ER? mediated Phd3 transcription. Manipulating ER? in vivo increases Phd3 transcription and reduces HIF-1 activity, while addition of PHD3 ameliorates adipose tissue fibrosis and inflammation. Our findings outline a novel regulatory relationship between E2/ER?, PHD3 and HIF-1 in adipose tissues, providing a mechanistic explanation for the protective effect of E2/ER? in adipose tissue.
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[Magnetic resonance imaging derived left ventricular global and region function parameters in healthy adults].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 05-17-2014
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To establish cardiac magnetic resonance imaging(MRI) derived left ventricular (LV) global and region function parameters in normal adults.
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Relationship between miRNA-338-3p expression and progression and prognosis of human colorectal carcinoma.
Chin. Med. J.
PUBLISHED: 05-15-2014
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miR-338-3p is a recently discovered miRNA and is involved in cell differentiation. However, few data are yet available on the aberrant expression of miR-338-3p in human colorectal carcinoma (CRC). This work aimed to investigate the relationship between miR-338-3p expression pattern and clinicopathological features of human CRC and the possible regulative mechanisms.
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Resveratrol levels and all-cause mortality in older community-dwelling adults.
JAMA Intern Med
PUBLISHED: 05-14-2014
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Resveratrol, a polyphenol found in grapes, red wine, chocolate, and certain berries and roots, is considered to have antioxidant, anti-inflammatory, and anticancer effects in humans and is related to longevity in some lower organisms.
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Oregonin from the Bark of Alnus japonica Restrained Ischemia-Reperfusion-Induced Mesentery Oxidative Stress by Inhibiting NADPH Oxidase Activation.
Microcirculation
PUBLISHED: 05-09-2014
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NADPH oxidase activation results in ROS overproduction that is the pathological basis of I/R injury. This study aimed to investigate potential effects of ORG on I/R-induced ROS production in rat mesenteric microvasculature and underlying mechanisms.
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Expression of natriuretic peptide receptor-A in esophageal squamous cell carcinomas and the relationship with tumor invasion and migration.
World J Surg Oncol
PUBLISHED: 05-06-2014
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The natriuretic peptide receptor-A (NPRA) has been investigated as a receptor of natriuretic peptides in the cardiovascular system. In this study, however, we analyze the expression status of NPRA and the relationship with tumor invasion in esophageal squamous cell carcinoma (ESCC) for the first time.
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Sensitive and rapid laser diagnostic for shock tube kinetics studies using cavity-enhanced absorption spectroscopy.
Opt Express
PUBLISHED: 05-03-2014
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We report the first application of cavity-enhanced absorption spectroscopy (CEAS) using a coherent light source for sensitive and rapid gaseous species time-history measurements in a shock tube. Off-axis alignment and fast scanning of the laser wavelength were used to minimize coupling noise in a low-finesse cavity. An absorption gain factor of 83 with a measurement time resolution of 20 µs was demonstrated for C2H2 detection using a near-infrared transition near 1537 nm, corresponding to a noise-equivalent detection limit of 20 ppm at 296 K and 76 ppm at 906 K at 50 kHz. This substantial gain in signal, relative to conventional single-pass absorption, will enable ultra-sensitive species detection in shock tube kinetics studies, particularly useful for measurements of minor species and for studies of dilute reactive systems.
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Frequency of supraventricular arrhythmias in patients with idiopathic pulmonary arterial hypertension.
Am. J. Cardiol.
PUBLISHED: 04-25-2014
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Supraventricular arrhythmias (SVA) may be risk factors of prognosis in patients with pulmonary arterial hypertension. SVA are increasingly reported in patients with pulmonary hypertension, but little is known about their incidence and outcomes for patients with idiopathic pulmonary arterial hypertension (IPAH) in a large cohort. In this 6-year prospective multicenter study, 280 patients with IPAH were enrolled to investigate the incidence of SVA and assess risk factors, clinical manifestation, management, and impact on survival. The cumulative 6-year incidence of SVA was 15.8%. The most common types of SVA were atrial fibrillation (n = 16) and atrial flutter (n = 13), followed by atrial tachycardia (n = 11). Most episodes of SVA were associated with significant clinical deterioration and right-sided cardiac failure. Sinus rhythm was successfully restored in most patients, resulting in clinical recovery. Increased right ventricular diameter, left atrial area, and higher right atrial pressure and pulmonary vascular resistance were associated with increased risk for experiencing SVA. SVA predicted a greater risk for mortality in a stepwise forward Cox analysis (hazard ratio 4.757, 95% confidence interval 2.695 to 8.397, p <0.001). Kaplan-Meier survival curves showed that patients with SVA, mainly permanent SVA, had a lower survival rate than those who did not develop SVA (p = 0.008). In conclusion, SVA often lead to clinical deterioration and may be associated with an increased risk for death in a large cohort of patients with IPAH. Restoration and maintenance of sinus rhythm are important treatment goals in patients with IPAH.
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Dietary intake of advanced glycation end products did not affect endothelial function and inflammation in healthy adults in a randomized controlled trial.
J. Nutr.
PUBLISHED: 04-17-2014
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When food is heated to high temperatures, the characteristic "browning" generates advanced glycation end products (AGEs). AGEs are associated with an increased risk of cardiovascular disease, diabetes, and other adverse outcomes. Whether dietary AGEs are absorbed and are harmful to human health remains highly controversial. The objective of this study was to compare the effects of a diet high or low in AGEs on endothelial function, circulating AGEs, inflammatory mediators, and circulating receptors for AGEs in healthy adults. A randomized, parallel-arm, controlled dietary intervention was conducted for 6 wk with 24 healthy adults, aged 50-69 y, that compared isocaloric, food-equivalent diets that were prepared at either high or mild temperatures. Peripheral arterial tonometry, serum and urine carboxymethyl-lysine (CML), inflammatory mediators (interleukin-6, C-reactive protein, vascular adhesion molecule-1, and tumor necrosis factor-? receptors I and II), soluble receptor for AGEs, and endogenous secretory receptor for AGEs were measured at baseline and after 6 wk of dietary intervention. In the low-AGE diet group, the following changed from baseline to 6 wk (mean ± SE): serum CML from 763 ± 24 to 679 ± 29 ng/mL (P = 0.03) and urine CML from 1.37 ± 1.47 to 0.77 ± 2.01 ?g/mL creatinine (P = 0.02). There were no significant changes in serum and urinary CML concentrations from baseline to follow-up in the high-AGE diet group. A high- or low-AGE diet had no significant impact on peripheral arterial tonometry or any inflammatory mediators after 6 wk of dietary intervention. In healthy middle-aged to older adults, consumption of a diet high or low in AGEs for 6 wk had no impact on endothelial function and inflammatory mediators, 2 precursors of cardiovascular disease.
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Frozen elephant trunk with total arch replacement for type A aortic dissections: Does acuity affect operative mortality?
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 04-16-2014
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We seek to compare the early outcomes of frozen elephant trunk with total aortic arch replacement using a 4-branched graft (the Sun procedure) in patients with acute and chronic type A aortic dissection (TAAD), identify the risk factors for operative mortality, and determine whether the acuity of TAAD significantly affects operative mortality.
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Autophagy inhibits chemotherapy-induced apoptosis through downregulating Bad and Bim in hepatocellular carcinoma cells.
Sci Rep
PUBLISHED: 04-15-2014
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The tumor microenvironment, including ischemia, has been increasingly recognized as a critical factor in the process of tumor development. Hypoxia and nutrient deficiency resulting from ischemia widely exist in solid tumors. Recent studies have shown that hypoxia and nutrient deficiency contribute to chemoresistance by inducing autophagy, but the underlying mechanism remains unknown. This study aimed to explore the role of autophagy induced by low glucose and hypoxia (LH) in the chemoresistance of hepatocellular carcinoma cells. Our results demonstrated that LH induced autophagy and downregulated Bad and Bim in hepatocellular carcinoma cells. The inhibition of autophagy reversed the reduction of these pro-apoptotic factors during the LH treatment. Furthermore, Bad and Bim were also significantly downregulated by autophagy during the process that LH promoted the chemoresistance of hepatocellular carcinoma cells. In addition, RNAi or the overexpression of Bad and Bim can significantly reduce or increase chemotherapy-induced cell death, respectively. Taken together, these data indicate that the downregulation of Bad and Bim plays a significant role in the autophagy-induced chemoresistance of hepatocellular carcinoma cells.
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Autophagy inhibition switches low-dose camptothecin-induced premature senescence to apoptosis in human colorectal cancer cells.
Biochem. Pharmacol.
PUBLISHED: 03-20-2014
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Recently, several studies indicated that senescent tumor cells are resistant to apoptosis in chemotherapy. They may return to cell cycle, thus act as stumbling blocks in anticancer treatments. In the present study, we found that, in human colorectal cancer cells, low-dose camptothecin (CPT) simultaneously induced autophagy and premature senescence through AMPK-TSC2-mTOR pathway and ATM-Chk2-p53-p21 pathway respectively. What's important is the suppression of autophagy substantially increased apoptosis and greatly attenuated senescence possibly by blocking p53/p21 pathway, which suggests that autophagy plays an indispensable role in sustaining cell senescence caused by low-dose CPT. The combination of low-dose CPT and autophagy inhibitor, a way to lead senescent cells to die, would be potentially valuable in cancer therapy.
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Icariside II improves cerebral microcirculatory disturbance and alleviates hippocampal injury in gerbils after ischemia-reperfusion.
Brain Res.
PUBLISHED: 03-18-2014
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the purpose of the present study was to examine the protective effect of Icariside II (IS) on cerebral microcirculatory disturbance and neuronal injury in hippocampal CA1 region induced by global cerebral I/R and the underlying mechanism.
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Therapeutic Benefit of Bortezomib on Acute Graft-versus-Host Disease is Tissue Specific and is Associated with Interleukin-6 Levels.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-15-2014
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Bortezomib, a proteasome inhibitor capable of direct antitumor effects, has been shown to prevent acute graft-versus-host disease (GVHD) when administered in a short course immediately after bone marrow transplantation (BMT) in mice. However, when bortezomib is given continuously, CD4(+) T cell-mediated gastrointestinal tract damage increases GVHD mortality. To investigate the protective effects of bortezomib on other organs, we used a CD8-dependent acute GVHD (aGVHD) model of C3H.SW donor T cells engrafted into irradiated C57BL/6 recipients (minor MHC mismatch), which lack significant gut GVHD. Our data in this model show that bortezomib can be given continuously to prevent and treat aGVHD mediated by CD8(+) T cells, but this effect is organ specific, such that only skin, and not liver, protection was observed. Despite the lack of hepatic protection, bortezomib still significantly improved survival, primarily because of its skin protection. Reduced skin GVHD by bortezomib was correlated with reduced serum and skin IL-6 levels. Administration of a blocking IL-6 antibody in this model also resulted in similar cutaneous GVHD protection. These results indicate that bortezomib or blockade of IL-6 may prevent CD8(+) T cell-mediated cutaneous acute GVHD.
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Posttreatment with ma-xing-shi-gan-tang, a chinese medicine formula, ameliorates lipopolysaccharide-induced lung microvessel hyperpermeability and inflammatory reaction in rat.
Microcirculation
PUBLISHED: 03-11-2014
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The aim of present study was to investigate the efficacy of MXSGT, a traditional Chinese medicine formula used for treatment of respiratory system diseases, in the LPS-induced rat ALI particularly with a focus on its effect on lung microvascular hyperpermeability and inflammatory reaction.
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Terminal supraparticle assemblies from similarly charged protein molecules and nanoparticles.
Nat Commun
PUBLISHED: 03-07-2014
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Self-assembly of proteins and inorganic nanoparticles into terminal assemblies makes possible a large family of uniformly sized hybrid colloids. These particles can be compared in terms of utility, versatility and multifunctionality to other known types of terminal assemblies. They are simple to make and offer theoretical tools for designing their structure and function. To demonstrate such assemblies, we combine cadmium telluride nanoparticles with cytochrome C protein and observe spontaneous formation of spherical supraparticles with a narrow size distribution. Such self-limiting behaviour originates from the competition between electrostatic repulsion and non-covalent attractive interactions. Experimental variation of supraparticle diameters for several assembly conditions matches predictions obtained in simulations. Similar to micelles, supraparticles can incorporate other biological components as exemplified by incorporation of nitrate reductase. Tight packing of nanoscale components enables effective charge and exciton transport in supraparticles and bionic combination of properties as demonstrated by enzymatic nitrate reduction initiated by light absorption in the nanoparticle.
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Serum cystatin C levels are associated with coronary artery disease and its severity.
Clin. Biochem.
PUBLISHED: 03-06-2014
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Serum cystatin C has been established as a predictor of cardiovascular events. The aim of this study was to evaluate the role of cystatin C in determining the presence and the severity of patients with coronary artery disease (CAD).
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Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis.
Cell Metab.
PUBLISHED: 03-06-2014
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The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes remain unclear. Here we show that induction of the unfolded protein response transcription factor spliced X-box binding protein 1 (Xbp1s) in pro-opiomelanocortin (Pomc) neurons alone is sufficient to protect against diet-induced obesity as well as improve leptin and insulin sensitivity, even in the presence of strong activators of ER stress. We also demonstrate that constitutive expression of Xbp1s in Pomc neurons contributes to improved hepatic insulin sensitivity and suppression of endogenous glucose production. Notably, elevated Xbp1s levels in Pomc neurons also resulted in activation of the Xbp1s axis in the liver via a cell-nonautonomous mechanism. Together our results identify critical molecular mechanisms linking ER stress in arcuate Pomc neurons to acute leptin and insulin resistance as well as liver metabolism in diet-induced obesity and diabetes.
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Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance.
Nat Commun
PUBLISHED: 02-28-2014
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Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammation; however, which Tlr4-expressing cells mediate this effect is unknown. Here we show that mice deficient in hepatocyte Tlr4 (Tlr4LKO) exhibit improved glucose tolerance, enhanced insulin sensitivity and ameliorated hepatic steatosis despite the development of obesity after a high-fat diet (HFD) challenge. Furthermore, Tlr4LKO mice have reduced macrophage content in white adipose tissue, as well as decreased tissue and circulating inflammatory markers. In contrast, the loss of Tlr4 activity in myeloid cells has little effect on insulin sensitivity. Collectively, these data indicate that the activation of Tlr4 on hepatocytes contributes to obesity-associated inflammation and insulin resistance, and suggest that targeting hepatocyte Tlr4 might be a useful therapeutic strategy for the treatment of type 2 diabetes.
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Surface-grafted semiconductor layer prepared by surface initiated ring-opening polymerization of L-lysine NCA derivatives.
Chem Asian J
PUBLISHED: 02-21-2014
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Asymmetric and symmetric L-lysine N-carboxylic anhydrides based on perylene bisimide derivatives were successfully synthesized and grafted onto silicon wafers via surface-initiated ring-opening polymerization. The grafted n-type semiconductor film was flat and compact, and its thickness could be tuned by variation of the polymerization conditions.
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PPAR? in vagal neurons regulates high-fat diet induced thermogenesis.
Cell Metab.
PUBLISHED: 01-29-2014
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The vagus nerve innervates visceral organs providing a link between key metabolic cues and the CNS. However, it is not clear whether vagal neurons can directly respond to changing lipid levels and whether altered "lipid sensing" by the vagus nerve regulates energy balance. In this study, we systematically profiled the expression of all known nuclear receptors in laser-captured nodose ganglion (NG) neurons. In particular, we found PPAR? expression was reduced by high-fat-diet feeding. Deletion of PPAR? in Phox2b neurons promoted HFD-induced thermogenesis that involved the reprograming of white adipocyte into a brown-like adipocyte cell fate. Finally, we showed that PPAR? in NG neurons regulates genes necessary for lipid metabolism and those that are important for synaptic transmission. Collectively, our findings provide insights into how vagal afferents survey peripheral metabolic cues and suggest that the reduction of PPAR? in NG neurons may serve as a protective mechanism against diet-induced weight gain.
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Left ventricular hypertrophy, abnormal ventricular geometry and relative wall thickness are associated with increased risk of stroke in hypertensive patients among the Han Chinese.
Hypertens. Res.
PUBLISHED: 01-24-2014
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Our study aimed to explore whether left ventricular hypertrophy (LVH), abnormal LV geometry and relative wall thickness (RWT) are associated with an increased risk of stroke in a hypertensive Chinese population. This study included 462 stroke patients and 3808 non-stroke hypertensive patients. LVH was diagnosed using the criteria of LV mass ?49.2?g?m(-2.7) for men and 46.7?g?m(-2.7) for women. A partition value of 0.43 was used for RWT. LV geometric patterns (normal, concentric remodeling, concentric or eccentric hypertrophy) were calculated according to LVH and RWT. Logistic regression analyses were used to determine the odds ratio (OR) and 95% confidence intervals (CI) of LVH, LV geometry abnormality and RWT for stroke. Our study suggested that LVH was associated with increased stroke risk (adjusted OR, 1.52; 95% CI, 1.25-1.85; multivariate-adjusted OR, 1.43; 95% CI, 1.16-1.75) and that concentric hypertrophy carried the highest risk of stroke (adjusted OR, 1.62; 95% CI, 1.21-2.17), followed by eccentric hypertrophy (adjusted OR, 1.51; 95% CI, 1.12-2.03), with concentric remodeling ranked third (adjusted OR, 1.34; 95% CI, 1.01-1.80). RWT was associated with an increased risk of stroke and was independent of LVMI and other risk factors for stroke (adjusted OR, 3.97; 95% CI, 1.10-14.34). Our observations in Chinese patients with hypertension indicated that LVH was an important risk factor for stroke, LV geometry abnormality was related to the presence of stroke, concentric hypertrophy carried the highest risk of stroke in cases of abnormal LV geometry and that RWT was also a risk factor for stroke and was independent of LVMI and other stroke risk factors.
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A low prevalence of sarcomeric gene variants in a Chinese cohort with left ventricular non-compaction.
Heart Vessels
PUBLISHED: 01-04-2014
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Left ventricular non-compaction (LVNC) is genetically heterogeneous. It has been previously shown that LVNC is associated with defects in TAZ, DNTA, LDB3, YWHAE, MIB1, PRDM16, and sarcomeric genes. This study was aimed to investigate sarcomeric gene mutations in a Chinese population with LVNC. From 2004 to 2010, 57 unrelated Chinese patients with LVNC were recruited at Fuwai Hospital, Beijing, China. Detailed clinical evaluation was performed on the probands and available family members. DNA samples isolated from the peripheral blood of the index cases were screened for 10 sarcomeric genes, including MYH7, MYBPC3, MYL2, MYL3, MYH6, TNNC1, TNNT2, TNNI3, TPM1, and ACTC1. Seven heterozygous mutations (6 missense and 1 deletion) were identified in 7 (12 %) of the patients. These mutations were distributed among 4 genes, 4 in MYH7, and 1 each in ACTC1, TNNT2, and TPM1. Six of the mutations were novel and another one was reported previously. All mutations affected conserved amino acid residues and were predicted to alter the structure of the proteins by in silico analysis. No significant difference was observed between mutation-positive and mutation-negative patients with respect to clinical characteristics at baseline and mortality during follow-up. In conclusion, our study indicates that sarcomeric gene mutations are uncommon causes of LVNC in Chinese patients and genetic background of the disease may be divergent among the different races.
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Colonization on root surface by a phenanthrene-degrading endophytic bacterium and its application for reducing plant phenanthrene contamination.
PLoS ONE
PUBLISHED: 01-01-2014
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A phenanthrene-degrading endophytic bacterium, Pn2, was isolated from Alopecurus aequalis Sobol grown in soils contaminated with polycyclic aromatic hydrocarbons (PAHs). Based on morphology, physiological characteristics and the 16S rRNA gene sequence, it was identified as Massilia sp. Strain Pn2 could degrade more than 95% of the phenanthrene (150 mg · L(-1)) in a minimal salts medium (MSM) within 48 hours at an initial pH of 7.0 and a temperature of 30 °C. Pn2 could grow well on the MSM plates with a series of other PAHs, including naphthalene, acenaphthene, anthracene and pyrene, and degrade them to different degrees. Pn2 could also colonize the root surface of ryegrass (Lolium multiflorum Lam), invade its internal root tissues and translocate into the plant shoot. When treated with the endophyte Pn2 under hydroponic growth conditions with 2 mg · L(-1) of phenanthrene in the Hoagland solution, the phenanthrene concentrations in ryegrass roots and shoots were reduced by 54% and 57%, respectively, compared with the endophyte-free treatment. Strain Pn2 could be a novel and useful bacterial resource for eliminating plant PAH contamination in polluted environments by degrading the PAHs inside plants. Furthermore, we provide new perspectives on the control of the plant uptake of PAHs via endophytic bacteria.
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Female sex is associated with worse prognosis in patients with hypertrophic cardiomyopathy in China.
PLoS ONE
PUBLISHED: 01-01-2014
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Sex plays an important role in the clinical expression and prognosis of various cardiovascular diseases. This study was designed to observe the effects of sex on hypertrophic cardiomyopathy (HCM).
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Autophagy protects against palmitate-induced apoptosis in hepatocytes.
Cell Biosci
PUBLISHED: 01-01-2014
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Non-alcoholic fatty liver disease, one of the most common liver diseases, has obtained increasing attention. Palmitate (PA)-induced liver injury is considered a risk factor for the development of non-alcoholic fatty liver disease. Autophagy, a cellular degradative pathway, is an important self-defense mechanism in response to various stresses. In this study, we investigated whether autophagy plays a protective role in the progression of PA-induced hepatocytes injury.
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Ginsenoside Rb1 ameliorates lipopolysaccharide-induced albumin leakage from rat mesenteric venules by intervening in both trans- and paracellular pathway.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 12-19-2013
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Lipopolysaccharide (LPS) is one of the common pathogens which causes mesentery hyperpermeability and intestinal edema related diseases. This study evaluated whether ginsenoside Rb1 (Rb1), an ingredient of a Chinese medicine Panax ginseng, has beneficial effects on mesentery microvascular hyperpermeability induced by LPS and the underlying mechanisms. Male Wistar rats were continuously infused with LPS (5 mg/kg/hr) via the left jugular vein for 90 min. In some rats, Rb1 (5 mg/kg/hr) was administrated through the left jugular vein 30 min after LPS infusion. The dynamics of fluorescein isothiocynate-labeled albumin leakage from mesentery venules was assessed by intravital microscopy. Intestinal tissue edema was evaluated by hematoxylin and eosin staining. The number of caveolae in endothelial cells of microvessels was examined by electron microscopy. Confocal microscopy and Western blotting were applied to detect caveolin-1 (Cav-1) expression and phosphorylation, junction-related proteins, and concerning signaling proteins in intestinal tissues and human umbilical vein endothelial cells. LPS infusion evoked an increased albumin leakage from mesentery venules, which was significantly ameliorated by Rb1 post-treatment. Mortality and intestinal edema around microvessels were also reduced by Rb1. Rb1 decreased caveolae number in endothelial cells of microvessels. Cav-1 expression and phosphorylation, VE-Cadherin phosphorylation, ZO-1 degradation, nuclear factor-kappa B (NF-?B) activation and Src kinase phosphorylation were inhibited by Rb1. Rb1 ameliorated microvascular hyperpermeability after the onset of endotoxemia and improved intestinal edema through inhibiting caveolae formation and junction disruption, which was correlated to suppression of NF-?B and Src activation.
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MicroRNA-338-3p Inhibits Colorectal Carcinoma Cell Invasion and Migration by Targeting Smoothened.
Jpn. J. Clin. Oncol.
PUBLISHED: 11-25-2013
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To investigate the regulative effect of microRNA-338-3p on colorectal carcinoma cell invasion and migration.
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Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy.
Chin. Med. J.
PUBLISHED: 11-19-2013
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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes.
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High-precision tracking of brownian boomerang colloidal particles confined in quasi two dimensions.
Langmuir
PUBLISHED: 11-11-2013
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In this article, we present a high-precision image-processing algorithm for tracking the translational and rotational Brownian motion of boomerang-shaped colloidal particles confined in quasi-two-dimensional geometry. By measuring mean square displacements of an immobilized particle, we demonstrate that the positional and angular precision of our imaging and image-processing system can achieve 13 nm and 0.004 rad, respectively. By analyzing computer-simulated images, we demonstrate that the positional and angular accuracies of our image-processing algorithm can achieve 32 nm and 0.006 rad. Because of zero correlations between the displacements in neighboring time intervals, trajectories of different videos of the same particle can be merged into a very long time trajectory, allowing for long-time averaging of different physical variables. We apply this image-processing algorithm to measure the diffusion coefficients of boomerang particles of three different apex angles and discuss the angle dependence of these diffusion coefficients.
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Effect of Exogenous Factors on Bacteriocin Production from Lactobacillus paracasei J23 by Using a Resting Cell System.
Int J Mol Sci
PUBLISHED: 10-17-2013
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A resting cell system was developed for bacteriocin Lac-B23 production from Lactobacillus paracasei J23. The resting cell medium contained (g/L): Glucose 20, Sodium acetate 5.0, MnSO4 0.25 MgSO4 0.5, Ammoniumhydrogencitrate 1.0, KH2PO4 1.0. The resting cell incubation time and temperature were 20 h and 37 °C and the effects of exogenous factors, including amino acids, glycerol, pyruvic acid, and ?-ketoglutaric acid were investigated. Cys and Gly could stimulate the production of bacteriocin, while no stimulus effect was observed for Glu, Tyr and Ala. Glycerol and pyruvic acid increased bacteriocin production and the optimum concentrations were 1% and 30 g/L, respectively. Bacteriocin could act as an inducer of its own biosynthesis. These findings are of importance for the further study of bacteriocin biosynthesis regulation and for the improvement of bacteriocin production yields.
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Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy.
Circ Cardiovasc Genet
PUBLISHED: 10-14-2013
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Background- Although mutations of several genes are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), the exact correlation between genotype and ventricular arrhythmia features remains unclear. This study was aimed to examine the possible association of the 9 known genes of ARVC with clinical and electrophysiological characteristics. Methods and Results- Ninety subjects diagnosed with ARVC who underwent electrophysiological study were recruited for screening the 9 known ARVC-causing genes. A total of 53 mutations were identified in 57 (63%) subjects. Mutation carriers had more frequent clinical ventricular tachycardia (VT; 89% versus 55%; P<0.001) and negative T waves in V1 to V3 (61% versus 33%; P=0.016). Subjects with plakophilin-2 (PKP2) mutations also had more frequent VT than those without mutations in PKP2. Comparison between subjects with multiple and single mutations showed that syncope occurred more often in the former group (58% versus 24%; P=0.018). VT was significantly more often induced in mutation carriers compared with noncarriers (75% versus 39%; P=0.001), as well as in PKP2 mutation carriers compared with subjects without PKP2 mutations (80% versus 48%; P=0.002). Induced VT with a rate ?200 bpm was more often documented in mutation carriers (88% versus 54%; P=0.013), as well as in PKP2 mutation carriers (91% versus 67%; P=0.041). Conclusions- Pathogenic gene mutations were found in nearly two thirds of subjects diagnosed with ARVC. Mutation carriers, especially PKP2, had a higher proportion of a history of VT and more inducible fast VT.
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Copper-Catalyzed Intermolecular Dehydrogenative Amidation/Amination of Quinoline N-Oxides with Lactams/Cyclamines.
Org. Lett.
PUBLISHED: 10-04-2013
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C-H, N-H dehydrogenative coupling of quinoline N-oxides with lactams/cyclamines has been achieved in the presence of the Cu(OAc)2 catalyst to give good to excellent yields. This study provides a new strategy for the construction of a 2-aminoquinoline skeleton via direct functionalization of aryl C-H bonds.
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Experimental recovery of quantum correlations in absence of system-environment back-action.
Nat Commun
PUBLISHED: 09-23-2013
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Revivals of quantum correlations in composite open quantum systems are a useful dynamical feature against detrimental effects of the environment. Their occurrence is attributed to flows of quantum information back and forth from systems to quantum environments. However, revivals also show up in models where the environment is classical, thus unable to store quantum correlations, and forbids system-environment back-action. This phenomenon opens basic issues about its interpretation involving the role of classical environments, memory effects, collective effects and system-environment correlations. Moreover, an experimental realization of back-action-free quantum revivals has applicative relevance as it leads to recover quantum resources without resorting to more demanding structured environments and correction procedures. Here we introduce a simple two-qubit model suitable to address these issues. We then report an all-optical experiment which simulates the model and permits us to recover and control, against decoherence, quantum correlations without back-action. We finally give an interpretation of the phenomenon by establishing the roles of the involved parties.
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Ratiometric luminescent detection of bacterial spores with terbium chelated semiconducting polymer dots.
Anal. Chem.
PUBLISHED: 09-20-2013
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We report a ratiometric fluorescent sensor based on semiconducting polymer dots chelated with terbium ions to detect bacterial spores in aqueous solution. Fluorescent polyfluorene (PFO) dots serve as a scaffold to coordinate with lanthanide ions that can be sensitized by calcium dipicolinate (CaDPA), an important biomarker of bacterial spores. The absorption band of PFO dots extends to deep UV region, allowing both the reference and the sensitizer can be excited with a single wavelength (~275 nm). The fluorescence of PFO remains constant as a reference, while the Tb(3+) ions exhibit enhanced luminescence upon binding with DPA. The sharp fluorescence peaks of ?-phase PFO dots and the narrow-band emissions of Tb(3+) ions enable ratiometric and sensitive CaDPA detection with a linear response over nanomolar concentration and a detection limit of ~0.2 nM. The Pdots based sensor also show excellent selectivity to CaDPA over other aromatic ligands. Our results indicate that the Tb(3+) chelated Pdots sensor is promising for sensitive and rapid detection of bacterial spores.
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Control of interface order by inverse quasi-epitaxial growth of squaraine/fullerene thin film photovoltaics.
ACS Nano
PUBLISHED: 09-09-2013
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It has been proposed that interface morphology affects the recombination rate for electrons and holes at donor-acceptor heterojunctions in thin film organic photovoltaic cells. The optimal morphology is one where there is disorder at the heterointerface and order in the bulk of the thin films, maximizing both the short circuit current and open circuit voltage. We show that an amorphous, buried functionalized molecular squaraine donor layer can undergo an "inverted" quasi-epitaxial growth during postdeposition processing, whereby crystallization is seeded by a subsequently deposited self-assembled nanocrystalline acceptor C60 cap layer. We call this apparently unprecedented growth process from a buried interface "inverse quasi-epitaxy" where the crystallites of these "soft" van der Waals bonded materials are only approximately aligned to those of the cap. The resulting crystalline interface hastens charge recombination, thereby reducing the open circuit voltage in an organic photovoltaic cell. The lattice registration also facilitates interdiffusion of the squaraine donor and C60 acceptor, which dramatically improves the short circuit current. By controlling the extent to which this crystallization occurs, the voltage losses can be minimized, resulting in power conversion efficiencies of ?P = 5.4 ± 0.3% for single-junction and ?P = 8.3 ± 0.4% for tandem small-molecule photovoltaics. This is a general phenomenon with implications for all organic donor-acceptor junctions. That is, epitaxial relationships typically result in a reduction in open circuit voltage that must be avoided in both bilayer and bulk heterojunction organic photovoltaic cells.
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Laminated nanotapes fabricated from conformation specific self-assembly of N-annulated perylene derivatives.
Chem. Commun. (Camb.)
PUBLISHED: 08-30-2013
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Laminated nanotapes were fabricated via conformation specific self-assembly of two N-annulated perylene derivatives (NPDs). The assemblies in solvated states were characterized using cryogenic transmission electron microscopy (cryo-TEM), and their nanostructures were modulated by the synergistic interactions of ?-? stacking and hydrogen bonds.
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Suns procedure of total arch replacement using a tetrafurcated graft with stented elephant trunk implantation: analysis of early outcome in 398 patients with acute type A aortic dissection.
Ann Cardiothorac Surg
PUBLISHED: 08-20-2013
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Acute type A aortic dissection (AAAD) remains one of the most lethal conditions requiring surgical repair, and is associated with a high rate of postoperative mortality and morbidity. Despite the satisfactory clinical outcomes achieved with the frozen elephant trunk technique so far, controversies still exist regarding the use of this aggressive approach in patients with AAAD. In this study, we seek to analyze the early outcomes of the Suns procedure, which is an approach integrating total arch replacement using a 4-branched graft with implantation of a special stented graft in the descending aorta, and identify the risk factors for postoperative mortality and morbidity of the Suns procedure in patients with AAAD.
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Fibrosis and adipose tissue dysfunction.
Cell Metab.
PUBLISHED: 08-15-2013
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Fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1? that in turn leads to a potent profibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an equally important role on systemic metabolic alterations as fibrotic conditions play in the liver, heart, and kidney. Here, we discuss recent advances in our understanding of the genesis, modulation, and systemic impact of excessive extracellular matrix (ECM) accumulation in adipose tissue of both rodents and humans and the ensuing impact on metabolic dysfunction.
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Self-assembly of copper sulfide nanoparticles into nanoribbons with continuous crystallinity.
ACS Nano
PUBLISHED: 08-12-2013
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Copper chalcogenide nanoparticles (NPs) represent a promising material for solar energy conversion, electrical charge storage, and plasmonic devices. However, it is difficult to achieve high-quality NP dispersions in experimentally convenient and technologically preferred aqueous media. Also problematic is the transition from NP dispersion to continuously crystalline nanoscale materials, for instance, nanowires, nanoribbons, or similar high aspect ratio nano/microstructures capable of charge transport necessary for such applications. All previous examples of copper sulfide assemblies contained insulating gaps between NPs. Here we show that aqueous synthesis of high-quality monodispersed high-chalcocite ?-Cu2S NPs, with sizes from 2 to 10 nm, is possible. When reaction time increased, the NP shape evolved from nearly spherical particles into disks with predominantly hexagonal shape. Moreover, the monodispersed ?-Cu2S NPs were found to spontaneously self-assemble into nanochains and, subsequently, to nanoribbons. The width and length of the nanoribbons were 4-20 nm and 50-950 nm, respectively, depending on the assembly conditions. We observed the formation of the nanoribbons with continuous crystal lattice and charge transport pathways, making possible the utilization of self-assembly processes in the manufacturing of photovoltaic, plasmonic, and charge storage devices.
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