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Find video protocols related to scientific articles indexed in Pubmed.
[Study of low radiation exposure dose and low contrast medium dose in coronary CT angiography with High-pitch spiral acquisition mode of dual source CT].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 11-14-2014
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To evaluate the feasibility of low radiation exposure and low contrast medium volume for coronary CT angiography with High- pitch spiral acquisition mode of dual source CT.
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[Effect of advanced glycosylation end products on oxidative stress and MCP-1 in human renal mesangial cells].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 10-22-2014
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To investigate the effects of advanced glycosylation end products(AGEs)modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs).
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Regional optimal allocation for reducing waste loads via artificial neural network and particle swarm optimization: a case study of ammonia nitrogen in Harbin, northeast China.
Water Sci. Technol.
PUBLISHED: 10-18-2014
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Cutting external waste loads can improve water quality. Allocation for reducing waste loads should consider changing variables, such as river flows and pollutant emissions. A particle swarm optimization (PSO) method and coupling artificial neural network (ANN) models have been applied to optimize reduction rates of ammonia nitrogen (NH3-N) loads from sewage outlets in Harbin, northeast China. For the planned water quality functional section (WQFS), the NH3-N concentration is related to emitted pollutant loads and can be well predicted by ANN linkage models. Further, NH3-N load reduction rates of all outlets are optimized by PSO with the water quality standard target. The highest NH3-N concentrations occur in January and February, a typical low-flow period in Harbin. The results delivered optimum NH3-N reduction rates for the five outlets, for January and February 2011. All predicted NH3-N concentrations after the reduction meet the water quality standard. The results indicate that the outlet with the highest NH3-N load has the biggest reduction rate in each WQFS, and outlets in the WQFS with higher background NH3-N concentrations need to cut more NH3-N loads. Decision-makers should not only focus on the outlet with the highest NH3-N emission load, but also ensure that the NH3-N concentration of upper WQFS meets the water quality goal.
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The enhanced photothermal effect of graphene/conjugated polymer composites: photoinduced energy transfer and applications in photocontrolled switches.
Chem. Commun. (Camb.)
PUBLISHED: 10-08-2014
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Composites prepared by grafting poly(3-hexylthiophene) (P3HT) onto the surfaces of reduced graphene oxide (RGO) (RGO-g-P3HT) exhibit an enhanced photothermal effect due to photoinduced energy transfer from P3HT to RGO. A remote photo-controlled electrical switch was prepared using RGO-g-P3HT as a photothermal layer.
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Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm.
Arch. Pharm. Res.
PUBLISHED: 09-23-2014
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Baicalin, a flavonoid, has a wide range of pharmacological properties, including immunomodulation. The objective of this study was to investigate the effect of baicalin on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in a colitis model. The rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baicalin (10 ml/kg, each) or mesalazine (positive control) was then administered orally for 7 days. Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. Our study showed that baicalin not only significantly attenuated TNBS-induced colitis by reducing the disease activity index as well as macroscopic and microscopic scores, but it also improved the weight loss and shortening of the colon. Baicalin treatment also induced a significant decrease in the levels of inflammatory mediators, including the myeloperoxidase activity, the levels of tumor necrosis factor ?, IL-1?, and Th1-related cytokines IL-12 and IFN-?. Furthermore, the beneficial effects of baicalin seem to be associated with regulation of the Th17 and Treg paradigm. We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor ?t. In contrast, there was an increase in Treg cells numbers, Treg-related cytokines transforming growth factor-? and IL-10, and forkhead box P3. Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis.
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Adrenergic signaling promotes angiogenesis through endothelial cell-tumor cell crosstalk.
Endocr. Relat. Cancer
PUBLISHED: 09-03-2014
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Angiogenesis is an important factor in invasive tumor growth, progression, and metastasis. Multiple proangiogenic mechanisms are involved in tumor angiogenesis. In this study, we showed that the neurotransmitter norepinephrine upregulated VEGF (VEGFA) expression in breast cancer cells and that the culture supernatant from norepinephrine-treated breast cancer cells promoted the formation of the capillary-like network of endothelial cells. However, the effects of norepinephrine were further enhanced when the endothelial cells were cocultured with breast cancer cells, indicating a critical role of tumor cell-endothelial cell contacts in norepinephrine-induced tumor angiogenesis. Interestingly, norepinephrine dramatically induced the activation of the Notch pathway, which is a cell-contact-mediated intercellular signaling pathway and tightly linked to tumor cell-stromal cell interaction and angiogenesis, in the endothelial cells that had been cocultured with breast cancer cells. Furthermore, the expression of the Notch ligand Jagged 1 was significantly upregulated by norepinephrine at both mRNA and protein levels in breast cancer cells. Inhibitors of ?2-adrenergic receptor (?2-AR), protein kinase A (PKA), and mTOR could reverse norepinephrine-induced Jagged 1 upregulation, indicating that the ?2-AR-PKA-mTOR pathway participates in this process. Knockdown of Jagged 1 expression in breast cancer cells not only repressed norepinephrine-induced activation of the Notch pathway in cocultured endothelial cells but also evidently impaired the effects of norepinephrine on capillary-like sprout formation. These data demonstrate that tumor angiogenesis mediated by the Jagged 1/Notch intercellular signaling is governed by the norepinephrine-activated ?2-AR-PKA-mTOR pathway.
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Using an improved Source Directional Apportionment method to quantify the PM2.5 source contributions from various directions in a megacity in China.
Chemosphere
PUBLISHED: 09-02-2014
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The transport of particulate matter (PM) and chemical species is an essential mechanism for determining the fate of PM pollutants and their effects. To determine source transport quantitatively, an ambient PM2.5 dataset from a megacity in China was analysed using a novel method called "Source Directional Apportionment" (SDA). The SDA method is developed in this work to quantify contributions of each source category from various directions. The three steps of SDA are (1) to estimate source categories and time series of source contributions to PM with a factor analysis model, (2) to identify directions by trajectory cluster analysis and (3) to quantify source directional contributions for each source category by combining the time series of source contributions to the back trajectories in each direction. For PM2.5 in Chengdu, crustal dust, vehicular exhaust, coal combustion and secondary sulphate are all important contributors to PM; secondary nitrate and cement dust are relatively less influential. Four potential source directions were identified in Chengdu during the sampling period from 2009 to 2011. The percentages of source directional contributions from Directions 1-4 (northeast, southwest to south, southwest and west) were estimated as follows: crustal dust (7.9%, 9.1%, 6.4% and 6.2%, respectively), cement dust (1.0%, 1.2%, 1.3% and 1.1%, respectively), vehicular exhaust (6.4%, 6.0%, 5.6% and 7.0%, respectively), secondary sulphate (5.1%, 5.2%, 5.6% and 8.6%, respectively) and secondary nitrate (2.0%, 2.4%, 2.5% and 2.3%, respectively). Finally, the source directional contributions to important chemical species were quantified to determine their transport from sources to receptor.
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Human Stem Cell-Derived Cardiomyocytes in Cellular Impedance Assays: Bringing Cardiotoxicity Screening to the Front Line.
Cardiovasc. Toxicol.
PUBLISHED: 08-19-2014
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Cardiovascular (CV) toxicity is a leading cause of drug attrition and withdrawal. Introducing in vitro assays with higher throughput should permit earlier CV hazard identification and enable medicinal chemists to design-out liabilities. Heretofore, development of in vitro CV assays has been limited by the challenge of replicating integrated cardiovascular physiology while achieving the throughput and consistency required for screening. These challenges appear to be met with a combination of human stem cell-derived cardiomyocytes (CM) which beat spontaneously and monitoring the response with technology that can assess drug-induced changes in voltage dependent contraction such as cellular impedance which has been validated with excellent predictivity for drug-induced arrhythmia and contractility. Here, we review advances in cardiomyocyte impedance with emphasis on stem cell-derived cardiomyocyte models for toxicity screening. Key perspectives include: the electrical principles of impedance technology, impedance detection of cardiomyocyte beating, beat parameter selection/analysis, validation in toxicity and drug discovery, and future directions. As a conclusion, an in vitro screening cascade is proffered using the downstream, inclusive detection of CM impedance assays as a primary screen followed by complementary CM assays chosen to enable mechanism-appropriate follow-up. The combined approach will enhance testing for CV liabilities prior to traditional in vivo models.
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Three-dimensional fluorescence excitation-emission matrix (EEM) spectroscopy with regional integration analysis for assessing waste sludge hydrolysis treated with multi-enzyme and thermophilic bacteria.
Bioresour. Technol.
PUBLISHED: 08-15-2014
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The hydrolysis effect of waste sludge after multi-enzyme and thermophilic bacteria pretreatments is investigated using excitation-emission matrix (EEM) with fluorescence regional integration (FRI) in this study. The compositional characteristics of extracellular polymeric substances (EPS) and dissolved organic matters (DOM) were analyzed to evaluate the sludge disintegration. The EPS and cell wall in sludge were disrupted after hydrolysis which led to carbohydrate, protein and soluble chemical oxygen demand (SCOD) of DOM increasing in sludge supernatant. The bio-degradability level in the extracted fractions of EPS and DOM depending on the fluorescence zones was found after hydrolysis. The highest proportion of percent fluorescence response (Pi,n) in EPS and DOM was soluble microbial by-product and humic acid-like organics. A significant increase of humic acid-like organics in DOM after thermophilic bacteria hydrolysis was obtained. The assessment of hydrolysis using EEM coupled with FRI provided a new insight toward the bio-utilization process of waste sludge.
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Overexpression of oxidored-nitro domain containing protein 1 induces growth inhibition and apoptosis in human prostate cancer PC3 cells.
Oncol. Rep.
PUBLISHED: 08-14-2014
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Previous studies have reported that oxidored-nitro domain containing protein 1 (NOR1) is a novel tumor suppressor gene identified in various types of cancer, such as nasopharyngeal carcinoma and cervical cancer. Recent studies have shown that NOR1 expression is lower in prostate cancer compared with normal prostate tissue. However, the specific function and exact mechanism of NOR1 in prostate cancer remains to be clarified. The present study aimed to investigate the function and mechanism of NOR1 in prostate cancer PC3 cells. DU145 and PC3 cells were transduced with a vector and cell viability, proliferation and apoptosis were determined. As predicted, NOR1 overexpression significantly inhibited growth and apoptosis in PC3 cells. NOR1 overexpression decreased the expression of the anti-apoptotic genes Bcl-2 and Bcl-xl and increased the level of the pro-apoptotic genes Bax and Bak in PC3 cells. Further investigation demonstrated that NOR1 overexpression activates caspase-3. Silencing of NOR1 did not inhibit growth or induce apoptosis in PC3 cells. Moreover, NOR1 inhibited proliferation and induced apoptosis via the activation of MAPK. The overexpression of NOR1 significantly inhibited tumor growth in PC3 tumor-bearing nude mice. The results suggest that the upregulated NOR1 expression was able to inhibit the progression of prostate cancer. Thus, NOR1 may be an ideal target for the treatment of prostate cancer.
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Design and implementation of a RF powering circuit for RFID tags or other batteryless embedded devices.
Sensors (Basel)
PUBLISHED: 08-13-2014
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A RF powering circuit used in radio-frequency identification (RFID) tags and other batteryless embedded devices is presented in this paper. The RF powering circuit harvests energy from electromagnetic waves and converts the RF energy to a stable voltage source. Analysis of a NMOS gate-cross connected bridge rectifier is conducted to demonstrate relationship between device sizes and power conversion efficiency (PCE) of the rectifier. A rectifier with 38.54% PCE under normal working conditions is designed. Moreover, a stable voltage regulator with a temperature and voltage optimizing strategy including adoption of a combination resistor is developed, which is able to accommodate a large input range of 4 V to 12 V and be immune to temperature variations. Latch-up prevention and noise isolation methods in layout design are also presented. Designed with the HJTC 0.25 ?m process, this regulator achieves 0.04 mV/°C temperature rejection ratio (TRR) and 2.5 mV/V voltage rejection ratio (VRR). The RF powering circuit is also fabricated in the HJTC 0.25 ?m process. The area of the RF powering circuit is 0.23 × 0.24 mm². The RF powering circuit is successfully integrated with ISO/IEC 15693-compatible and ISO/IEC 14443-compatible RFID tag chips.
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A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation.
Nat Commun
PUBLISHED: 08-08-2014
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Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen ((1)O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce (1)O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of (1)O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility.
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Egg consumption is associated with increased risk of ovarian cancer: Evidence from a meta-analysis of observational studies.
Clin Nutr
PUBLISHED: 07-23-2014
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The findings of epidemiologic studies on the association between egg consumption and ovarian cancer risk remain conflicting. The aim of this meta-analysis was to investigate whether an association exists between egg intake and ovarian cancer risk in epidemiologic studies.
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Examining the Protective Role of ErbB2 Modulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Toxicol. Sci.
PUBLISHED: 07-23-2014
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Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from maturing hiPSC-CMs detected expression of ?570 signaling proteins. EGFR/ErbB1, HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor receptor family were confirmed by Western blot. Activation of ErbB signaling by neuregulin-1? (NRG, a natural ligand for ErbB4) and its modulation by trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real-time cellular impedance analysis and ATP measurement. Collectively, these results support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and support the value of using these cells in early assessments of cardiotoxicity or efficacy.
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Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice.
EMBO Mol Med
PUBLISHED: 07-20-2014
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Plasma high-density lipoprotein (HDL) levels show a strong inverse correlation with atherosclerotic vascular disease. Previous studies have demonstrated that antagonism of miR-33 in vivo increases circulating HDL and reverse cholesterol transport (RCT), thereby reducing the progression and enhancing the regression of atherosclerosis. While the efficacy of short-term anti-miR-33 treatment has been previously studied, the long-term effect of miR-33 antagonism in vivo remains to be elucidated. Here, we show that long-term therapeutic silencing of miR-33 increases circulating triglyceride (TG) levels and lipid accumulation in the liver. These adverse effects were only found when mice were fed a high-fat diet (HFD). Mechanistically, we demonstrate that chronic inhibition of miR-33 increases the expression of genes involved in fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the livers of mice treated with miR-33 antisense oligonucleotides. We also report that anti-miR-33 therapy enhances the expression of nuclear transcription Y subunit gamma (NFYC), a transcriptional regulator required for DNA binding and full transcriptional activation of SREBP-responsive genes, including ACC and FAS. Taken together, these results suggest that persistent inhibition of miR-33 when mice are fed a high-fat diet (HFD) might cause deleterious effects such as moderate hepatic steatosis and hypertriglyceridemia. These unexpected findings highlight the importance of assessing the effect of chronic inhibition of miR-33 in non-human primates before we can translate this therapy to humans.
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Event-based user classification in Weibo media.
ScientificWorldJournal
PUBLISHED: 07-16-2014
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Weibo media, known as the real-time microblogging services, has attracted massive attention and support from social network users. Weibo platform offers an opportunity for people to access information and changes the way people acquire and disseminate information significantly. Meanwhile, it enables people to respond to the social events in a more convenient way. Much of the information in Weibo media is related to some events. Users who post different contents, and exert different behavior or attitude may lead to different contribution to the specific event. Therefore, classifying the large amount of uncategorized social circles generated in Weibo media automatically from the perspective of events has been a promising task. Under this circumstance, in order to effectively organize and manage the huge amounts of users, thereby further managing their contents, we address the task of user classification in a more granular, event-based approach in this paper. By analyzing real data collected from Sina Weibo, we investigate the Weibo properties and utilize both content information and social network information to classify the numerous users into four primary groups: celebrities, organizations/media accounts, grassroots stars, and ordinary individuals. The experiments results show that our method identifies the user categories accurately.
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Modulation of frustration in folding by sequence permutation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-07-2014
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Folding of globular proteins can be envisioned as the contraction of a random coil unfolded state toward the native state on an energy surface rough with local minima trapping frustrated species. These substructures impede productive folding and can serve as nucleation sites for aggregation reactions. However, little is known about the relationship between frustration and its underlying sequence determinants. Chemotaxis response regulator Y (CheY), a 129-amino acid bacterial protein, has been shown previously to populate an off-pathway kinetic trap in the microsecond time range. The frustration has been ascribed to premature docking of the N- and C-terminal subdomains or, alternatively, to the formation of an unproductive local-in-sequence cluster of branched aliphatic side chains, isoleucine, leucine, and valine (ILV). The roles of the subdomains and ILV clusters in frustration were tested by altering the sequence connectivity using circular permutations. Surprisingly, the stability and buried surface area of the intermediate could be increased or decreased depending on the location of the termini. Comparison with the results of small-angle X-ray-scattering experiments and simulations points to the accelerated formation of a more compact, on-pathway species for the more stable intermediate. The effect of chain connectivity in modulating the structures and stabilities of the early kinetic traps in CheY is better understood in terms of the ILV cluster model. However, the subdomain model captures the requirement for an intact N-terminal domain to access the native conformation. Chain entropy and aliphatic-rich sequences play crucial roles in biasing the early events leading to frustration in the folding of CheY.
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Cytosolic phosphorylating glyceraldehyde-3-phosphate dehydrogenases affect Arabidopsis cellular metabolism and promote seed oil accumulation.
Plant Cell
PUBLISHED: 07-02-2014
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The cytosolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPC) catalyzes a key reaction in glycolysis, but its contribution to plant metabolism and growth are not well defined. Here, we show that two cytosolic GAPCs play important roles in cellular metabolism and seed oil accumulation. Knockout or overexpression of GAPCs caused significant changes in the level of intermediates in the glycolytic pathway and the ratios of ATP/ADP and NAD(P)H/NAD(P). Two double knockout seeds had ?3% of dry weight decrease in oil content compared with that of the wild type. In transgenic seeds under the constitutive 35S promoter, oil content was increased up to 42% of dry weight compared with 36% in the wild type and the fatty acid composition was altered; however, these transgenic lines exhibited decreased fertility. Seed-specific overexpression lines had >3% increase in seed oil without compromised seed yield or fecundity. The results demonstrate that GAPC levels play important roles in the overall cellular production of reductants, energy, and carbohydrate metabolites and that GAPC levels are directly correlated with seed oil accumulation. Changes in cellular metabolites and cofactor levels highlight the complexity and tolerance of Arabidopsis thaliana cells to the metabolic perturbation. Further implications for metabolic engineering of seed oil production are discussed.
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Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing.
Nanoscale
PUBLISHED: 07-02-2014
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Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.
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Further insights into the composition, source and toxicity of pahs in size-resolved PM in a megacity in China.
Environ. Toxicol. Chem.
PUBLISHED: 07-01-2014
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Concentrations of PM10 and PM2.5 and 16 polycyclic aromatic hydrocarbons (PAHs) were measured. The average concentrations of PM10 and PM2.5 reached 209.75 ?g/m(3) and 141.87 ?g/m(3) ; and those of ?PAHs were 41.46 ng/m(3) for PM10 and 36.77 ng/m(3) for PM2.5 . The mass ratio concentrations were 219.23 ?g/g and 311.01 ?g/g in PM10 and PM2.5 , respectively. Three sources and their contributions for PAHs were obtained. For individual-input mode, diesel exhaust source contributed 46.77% (PM10 ) and 41.12% (PM2.5 ) for mass concentration; 48.69% (PM10 ) and 39.47% (PM2.5 ) for mass ratio concentration while gasoline exhaust source were 31.02% (PM10 ), 39.47% (PM2.5 ) and 28.95% (PM10 ), 36.46% (PM2.5 ), respectively for each concentration. As to coal combustion source, 22.22% and 19.41% to PM10 and PM2.5 for mass concentration, as well as 22.36% as 15.89% for mass ratio concentration, were observed. For combined-input mode, same source categories were obtained. Source contributions to PM10 and PM2.5 were diesel exhaust (40.70% and 36.64% for mass concentration; 49.19% and 38.47% for mass ratio concentration), gasoline exhaust (35.09% and 38.47%; 32.50% and 33.43%) and coal combustion (24.21% and 24.89%; 18.31% and18.17%). Source risk assessment showed that vehicle emission was a significant contributor. The findings can help elucidate sources of PAHs and provide good evidence for further applications of Unmix model and deeper studies about PAHs. This article is protected by copyright. All rights reserved.
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An update on overweight and obesity in rural Northeast China: from lifestyle risk factors to cardiometabolic comorbidities.
BMC Public Health
PUBLISHED: 06-28-2014
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Not enough is known about the prevalence of overweight and obesity in rural China in the current decade. We aim to update our knowledge of the prevalence of obesity and its associated risk factors and comorbidities in a large population sample in rural Northeast China.
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[Salvage surgery for neck recurrence or residue of nasopharyngeal carcinoma after primary radiotherapy].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 06-17-2014
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To investigate the surgical procedures and prognosis for neck recurrence or residue of nasopharyngeal carcinoma(NPC) after primary radiotherapy.
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Fine mapping of qHd1, a minor heading date QTL with pleiotropism for yield traits in rice (Oryza sativa L.).
Theor. Appl. Genet.
PUBLISHED: 06-16-2014
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A minor QTL for heading date located on the long arm of rice chromosome 1 was delimitated to a 95.0-kb region using near isogenic lines with sequential segregating regions. Heading date and grain yield are two key factors determining the commercial potential of a rice variety. In this study, rice populations with sequential segregating regions were developed and used for mapping a minor QTL for heading date, qHd1. A total of 18 populations in six advanced generations through BC2F6 to BC2F11 were derived from a single BC2F3 plant of the indica rice cross Zhenshan 97 (ZS97)///ZS97//ZS97/Milyang 46. The QTL was delimitated to a 95.0-kb region flanked by RM12102 and RM12108 in the terminal region of the long arm of chromosome 1. Results also showed that qHd1 was not involved in the photoperiodic response, having an additive effect ranging from 2.4 d to 2.9 d observed in near isogenic lines grown in the paddy field and under the controlled conditions of either short day or long day. The QTL had pleiotropic effects on yield traits, with the ZS97 allele delaying heading and increasing the number of spikelets per panicle, the number of grains per panicle and grain yield per plant. The candidate region contains ten annotated genes including two genes with functional information related to the control of heading date. These results lay a foundation for the cloning of qHd1. In addition, this kind of minor QTLs could be of great significance in rice breeding for allowing minor adjustment of heading date and yield traits.
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Sulfonated polystyrene magnetic nanobeads coupled with immunochromatographic strip for clenbuterol determination in pork muscle.
Talanta
PUBLISHED: 06-14-2014
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A magnetic solid-phase extraction method (MSPE) was developed to pre-concentrate and cleanup clenbuterol (CLE) from pork muscle. Novel sulfonated polystyrene magnetic nanobeads (spMNBs) were synthesized via a one-pot emulsion copolymerization method by using divinylbenzene, styrene, and sodium styrene sulfonate in the presence of oleic acid-modified and 10-undecylenic acid-modified magnetic ferrofluid. The resulting spMNBs exhibited high adsorption efficiency for CLE and for 10 other common beta-adrenergic agonists, namely, brombuterol, ractopamine, tulobuterol, bambuterol, cimbuterol, mabuterol, clorprenaline, penbutolol, salbutamol, and cimaterol. The adsorption behavior of the spMNBs for CLE was described by the Langmuir equation with a maximum adsorption capacity of 0.41 mg/g. Under the optimized parameters, the extraction of CLE from 0.5 g of pork muscle required 25mg of the spMNBs at a shortened adsorption time (0.5 min). The proposed MSPE was coupled with colloidal gold nanoparticle-based immunochromatographic assay (MSPE-AuNPIA) for the quantitative detection of CLE residue in pork muscle. The limit of detection and limit of quantification for the pork muscle were 0.10 and 0.24 ng/g, respectively. The intra-day and inter-day assay recoveries at three CLE spiked concentrations ranged from 92.5% to 98.1%, with relative standard deviations ranging from 3.2% to 13.0%. The results of MSPE-AuNPIA were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CLE values obtained with MSPE-AuNPIA agreed with those obtained with LC-MS/MS.
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Effects of hexavalent chromium on performance and microbial community of an aerobic granular sequencing batch reactor.
Environ Sci Pollut Res Int
PUBLISHED: 06-12-2014
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The performance and microbial community of an aerobic granular sequencing batch reactor (GSBR) were investigated at different hexavalent chromium (Cr(VI)) concentrations. The COD and NH4 (+)-N removal efficiencies decreased with the increase in Cr(VI) concentration from 0 to 30 mg/L. The specific oxygen utilization rate (SOUR) decreased from 34.86 to 12.18 mg/(g mixed liquor suspended sludge (MLSS)·h) with the increase in Cr(VI) concentration from 0 to 30 mg/L. The specific ammonium oxidation rate (SAOR), specific nitrite oxidation rate (SNOR), and specific nitrate reduction rate (SNRR) decreased with the increase in Cr(VI) concentration, whereas the SNRR was always higher than the sum of SAOR and SNOR at 0-30 mg/L Cr(VI). The scanning electron micrographs (SEM) showed some undefined particles on the surface of filamentous bacteria that might be the chelation of chromium and macromolecular organics at 30 mg/L Cr(VI). The denaturing gradient gel electrophoresis (DGGE) profiles revealed that some microorganisms adapting to high Cr(VI) concentration gradually became the predominant bacteria, while others without Cr(VI)-tolerance capacity tended to deplete or weaken. Some bacteria could tolerate the toxicity of high Cr(VI) concentration in the aerobic GSBR, such as Propionibacteriaceae bacterium, Ochrobactrum anthropi, and Micropruina glycogenica.
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Dual specificity phosphatase 6 suppresses the growth and metastasis of prostate cancer cells.
Mol Med Rep
PUBLISHED: 06-05-2014
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Dual specificity phosphatase 6 (DUSP6) is expressed at low levels in numerous types of human cancer. The loss of DUSP6 plays a pivotal role in tumor progression; however, the role of DUSP6 in prostate cancer remains unclear. In this study, in vitro invasion assays and in vivo metastasis experiments were used to investigate the effects of DUSP6 on prostate cancer cell invasion and metastasis. Furthermore, in vitro growth and soft agar assays and in vivo growth experiments were performed to determine the function of DUSP6 in cell proliferation. The results showed that the overexpression of DUSP6 suppressed the invasion and growth of DU?145 human prostate cancer cells, whereas knockdown of DUSP6 promoted the invasion and proliferation of LNCap human prostate adenocarcinoma cells. Further experiments demonstrated that the overexpression of DUSP6 inhibited the proliferation and liver metastasis of DU?145 cells in mice. In addition, DUSP6 downregulated the expression of matrix metallopeptidase 3 and interleukin 8 in prostate cancer cells. Taken together, these findings indicate that DUSP6 may act as a negative mediator in the regulation of prostate cancer cell growth and metastasis.
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Effect of Tiotropium on Heart Rate Variability in Stable Chronic Obstructive Pulmonary Disease Patients.
J Aerosol Med Pulm Drug Deliv
PUBLISHED: 05-21-2014
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Abstract Background: The chronic use of the long-acting anticholinergic agent, tiotropium, in chronic obstructive pulmonary disease (COPD) has been linked in some reports to an increase in adverse cardiovascular effects. Decreased heart rate variability (HRV) is a condition seen in COPD patients that has also been linked to poor cardiovascular outcome. We aimed in this study to investigate changes in HRV caused by tiotropium administration to COPD patients in order to determine whether changes occurred that might contribute to an increase in adverse cardiovascular events. Methods: Seventy patients with moderate-to-severe stable COPD were treated with once-daily dosing of tiotropium (two puffs of Spiriva Respimat, 2.5??g solution) for 3 months. HRV, pulmonary function, and quality of life were measured before and after 1 and 3 months of therapy. Results: Pulmonary function and quality of life improved significantly, after both 1 and 3 months of therapy. No significant change in HRV parameters occurred, except for a significant decrease in the high-frequency and increase in the low-frequency component of HRV at the 1-month assessment. Conclusion: Changes in HRV caused by tiotropium use are not sufficient to explain a possible increase in adverse cardiovascular events.
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Polymorphisms of leptin-b gene associated with growth traits in orange-spotted grouper (Epinephelus coioides).
Int J Mol Sci
PUBLISHED: 04-25-2014
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In mammals, leptin has been demonstrated to perform important roles in many physiological activities and to influence development, growth, metabolism and reproduction. However, in fish, its function is still unclear. Duplicate leptin genes, leptin-a and leptin-b, have been identified in the orange-spotted grouper. In the present study, the polymorphisms in the leptin-b gene of the orange-spotted grouper were detected, and the relation between these polymorphisms and 12 growth traits were analyzed. Six polymorphisms (including 3 single nucleotide polymorphisms (c.14G>A, c.93A>G, c.149G>A) in exon 1, 2 SNPs (c.181A>G, c.193G>A) in intron 1, and 1 SNP (c.360C>T) in exon 2) were identified and genotyped from 200 different individuals. The results revealed that the SNP c.149G>A was significantly associated with growth traits, that the heterozygous mutation genotype GA having negative effects on growth traits. However, the other five SNPs (c.14G>A, c.93A>G, c.181A>G, c.193G>A, c.360C>T) did not show significant associations with all the growth traits. Compared with our findings in leptin-a gene, the results suggested that the leptin-a hormone has more important physiological effects in fish bodies than the leptin-b type. Moreover, leptin genes were supposed to be one class of major candidate genes of regulating growth traits in the orange-spotted grouper.
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Ion Torrent next-generation sequencing reveals the complete mitochondrial genome of black and reddish morphs of the Coral Trout Plectropomus leopardus.
Mitochondrial DNA
PUBLISHED: 04-18-2014
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Abstract Using Ion Torrent next-generation sequencing (NGS) technology, we sequenced the complete mitochondrial genome (mitogenome) of black and reddish morphs of the coral trout Plectropomus leopardus. High-throughput sequencing generated a total of 958,614 sequence reads covering 164.80?Mb of two mitogenomes with a coverage of 4800X. Thirty-seven mitochondrial genes and gene order of P. leopardus was quite similar to that of other teleostean fishes. Most genes were either abutted or overlapped, and all the protein-coding genes began with an ATG start codon except for COX1 and ATP6. The number of stop codon was different for the black and reddish P. leopardus. Comparisons between the mitochondrial sequences of the two morphs revealed a total of 74 variable sites and one indel. Nucleotide diversity across protein-coding gene varied from 0.0006 (16s rRNA) to 0.0070 (Cytochrome b). As expected, the highest level of nucleotide diversity (0.0291) was detected in the control region. Our results demonstrate the NGS technology based on Ion torrent platform can be used to assemble the mitogenome of fish species.
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Suv39h1 mediates AP-2?-dependent inhibition of C/EBP? expression during adipogenesis.
Mol. Cell. Biol.
PUBLISHED: 04-14-2014
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Previous studies have shown that CCAAT/enhancer-binding protein ? (C/EBP?) plays a very important role during adipocyte terminal differentiation and that AP-2? (activator protein 2?) acts as a repressor to delay the expression of C/EBP?. However, the mechanisms by which AP-2? prevents the expression of C/EBP? are not fully understood. Here, we present evidence that Suv39h1, a histone H3 lysine 9 (H3K9)-specific trimethyltransferase, and G9a, a euchromatic methyltransferase, both interact with AP-2? and enhance AP-2?-mediated transcriptional repression of C/EBP?. Interestingly, we discovered that G9a mediates dimethylation of H3K9, thus providing the substrate, which is methylated by Suv39h1, to H3K9me3 on the C/EBP? promoter. The expression level of AP-2? was consistent with enrichment of H3K9me2 and H3K9me3 on the C/EBP? promoter in 3T3-L1 preadipocytes. Knockdown of Suv39h markedly increased C/EBP? expression and promoted adipogenesis. Conversely, ectopic expression of Suv39h1 delayed C/EBP? expression and impaired the accumulation of triglyceride, while simultaneous knockdown of AP-2? or G9a partially rescued this process. These findings indicate that Suv39h1 enhances AP-2?-mediated transcriptional repression of C/EBP? in an epigenetic manner and further inhibits adipocyte differentiation.
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Automated dispersive liquid-liquid microextraction-gas chromatography-mass spectrometry.
Anal. Chem.
PUBLISHED: 04-04-2014
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An innovative automated procedure, low-density solvent based/solvent demulsification dispersive liquid-liquid microextraction (automated DLLME) coupled to gas chromatography-mass spectrometry (GC/MS) analysis, has been developed. The most significant innovation of the method is the automation. The entire procedure, including the extraction of the model analytes (phthalate esters) by DLLME from the aqueous sample solution, breaking up of the emulsion after extraction, collection of the extract, and analysis of the extract by GC/MS, was completely automated. The applications of low-density solvent as extraction solvent and the solvent demulsification technique to break up the emulsion simplified the procedure and facilitated its automation. Orthogonal array design (OAD) as an efficient optimization strategy was employed to optimize the extraction parameters, with all the experiments conducted auotmatically. An OA16 (4(1) × 2(12)) matrix was initially employed for the identification of optimized extraction parameters (type and volume of extraction solvent, type and volume of dispersive solvent and demulsification solvent, demulsification time, and injection speed). Then, on the basis of the results, more levels (values) of five extraction parameters were investigated by an OA16 (4(5)) matrix and quantitatively assessed by the analysis of variance (ANOVA). Enrichment factors of between 178- and 272-fold were obtained for the phthalate esters. The linearities were in the range of 0.1 and 50 ?g/L and 0.2 and 50 ?g/L, depending on the analytes. Good limits of detection (in the range of 0.01 to 0.02 ?g/L) and satisfactory repeatability (relative standard deviations of below 5.9%) were obtained. The proposed method demonstrates for the first time integrated sample preparation by DLLME and analysis by GC/MS that can be operated automatically across multiple experiments.
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The influence of laser clipped by the laser entrance hole on hohlraum radiation measurement on Shenguang-III prototype.
Rev Sci Instrum
PUBLISHED: 04-03-2014
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Measuring the x-ray flux exiting the target's laser entrance hole (LEH) is the most common diagnostic that quantifies the x-ray intensity inside the laser-driven hohlraum. However, this signal accounts for only a small portion of the incident laser power and thus is likely to be affected by unwanted x-ray background from non-target area, leading to an overestimation of the hohlraum drive. Unwanted emission might be produced when the laser light is clipped by the LEH (LEH clipping) because of a lack of clearance for laser spot, or with a laser spot comprising of discrete structure, or even with a poor pointing accuracy. Its influence on the hohlraum radiation diagnostic is investigated on Shenguang-III prototype laser facility with the typical 1 ns square pulse. The experiment employed three types of targets to excite the unwanted x-ray background from LEH clipping, unconverted light, and both effects, respectively. This work gives an absolute evaluation of x-ray produced by the LEH clipping, which is measured by flat-response x-ray detectors (FXRD) at multiple view angles. The result indicates that there is little variation in measured emission to various view angles, because the unwanted x-rays are mainly generated at the side face of the LEH lip when laser is obliquely incident. Therefore, the LEH clipping brings more overestimation in hohlraum radiation measurement at larger view angle since the hohlraum LEH as an emitting source viewed by FXRD is decreased as the view angle increases. In our condition, the LEH clipping contributes 2%-3.5% overestimation to the hohlraum flux measurement.
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Zinc and autophagy.
Biometals
PUBLISHED: 03-14-2014
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Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the role of zinc in the regulation of autophagy, the role of autophagy in zinc metabolism, and the potential role of autophagy as a mediator of the protective effects of zinc. Data from in vitro studies consistently support the notion that zinc is critical for early and late autophagy. Studies have shown inhibition of early and late autophagy in cells cultured in medium treated with zinc chelators. Conversely, excess zinc added to the medium has shown to potentiate the stimulation of autophagy by tamoxifen, H2O2, ethanol and dopamine. The potential role of autophagy in zinc homeostasis has just begun to be investigated. Increasing evidence indicates that autophagy dysregulation causes significant changes in cellular zinc homeostasis. Autophagy may mediate the protective effect of zinc against lipid accumulation, apoptosis and inflammation by promoting degradation of lipid droplets, inflammasomes, p62/SQSTM1 and damaged mitochondria. Studies with humans and animal models are necessary to determine whether autophagy is influenced by zinc intake.
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Liver X receptor ? delays transformation of radial glial cells into astrocytes during mouse cerebral cortical development.
Neurochem. Int.
PUBLISHED: 03-02-2014
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Radial glial (RG) cells serve as stem cells to produce new born neurons and scaffolds for neuronal migration during corticogenesis. After neurogenesis and migration are completed, most RG cells transform into astrocytes. However, the mechanisms that determine how RG cells are transformed into astrocytes are not well understood. Using nestin as a specific marker for both RG cells and astrocytes, we found that loss of LXR? caused a reduction in the level of RG fibers and increase in the astrocytes. At the same time, we showed that the level of brain lipid-binding protein (BLBP), a RG-specific protein, was lower in the LXR? knockout (LXR?(-/-)) mice than in the wild type (WT) littermates from E18.5 to P14, a time period when most of RG cells are transformed into astrocytes. However, loss of LXR? induced significant increase in the number of GFAP labeled astrocytes in the cerebral cortex. An increase of the transformation of RG cells into astrocytes in LXR?(-/-) mice was further confirmed by the increased percentage of BLBP and GFAP double stained cells in the total BLBP positive cells of the Layer I and Layers V-VI. TGF-?1 and Smad4 are thought to be involved in the transformation of RG cells into astrocytes. The expression levels of TGF-?1mRNA and Smad4 mRNA were significantly higher in the cerebral cortex of LXR?(-/-) mice than that in the WT littermates at P2 and P7, but by P10 and P14, mRNA levels had normalized and no differences were observed between WT and LXR?(-/-) mice. Taken together, our findings suggest that loss of LXR? accelerates the transformation of RG cells into astrocytes and that this acceleration may be correlated to higher levels TGF-?1 and Smad4 in the cerebral cortex between P2 and P7.
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Physically constrained source apportionment (PCSA) for polycyclic aromatic hydrocarbon using the Multilinear Engine 2-species ratios (ME2-SR) method.
Sci. Total Environ.
PUBLISHED: 02-25-2014
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An improved physically constrained source apportionment (PCSA) technology using the Multilinear Engine 2-species ratios (ME2-SR) method was proposed and applied to quantify the sources of PM10- and PM2.5-associated polycyclic aromatic hydrocarbons (PAHs) from Chengdu in winter time. Sixteen priority PAH compounds were detected with mean ?PAH concentrations (sum of 16 PAHs) ranging from 70.65ng/m(3) to 209.58ng/m(3) and from 59.17ng/m(3) to 170.64ng/m(3) for the PM10 and PM2.5 samples, respectively. The ME2-SR and positive matrix factorization (PMF) models were employed to estimate the source contributions of PAHs, and these estimates agreed with the experimental results. For the PMF model, the highest contributor to the ?PAHs was vehicular emission (81.69% for PM10, 82.06% for PM2.5), followed by coal combustion (12.68%, 12.11%), wood combustion (5.65%, 4.45%) and oil combustion (0.72%, 0.88%). For the ME2-SR method, the highest contributions were from diesel (43.19% for PM10, 47.17% for PM2.5) and gasoline exhaust (34.94%, 32.44%), followed by wood combustion (8.79%, 6.37%), coal combustion (12.46%, 12.37%) and oil combustion (0.80%, 1.22%). However, the PAH ratios calculated for the factors extracted by ME2-SR were closer to the values from actual source profiles, implying that the results obtained from ME2-SR might be physically constrained and satisfactory.
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HTUPA as a new thrombolytic agent for acute myocardial infarction: a multicenter, randomized study.
Int. J. Cardiol.
PUBLISHED: 02-15-2014
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It is necessary to develop a new thrombolytic agent which can be used by a single bolus at first aid sites to decrease the time to reperfusion in clinical practice. HTUPA, a genetically engineered new thrombolytic with a longer half-life, is well qualified. We aim to compare the thrombolytic efficacy and safety of human tissue urokinase type plasminogen activator (HTUPA) to recombinant tissue plasminogen activator (rt-PA) in Chinese patients with acute myocardial infarction (AMI).
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[Erectile dysfunction in men with lower urinary tract symptoms].
Zhonghua Nan Ke Xue
PUBLISHED: 02-14-2014
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To investigate the incidence of erectile dysfunction (ED) in men with lower urinary tract symptoms (LUTS) and the correlation between LUTS and ED.
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Association of miR-146a gene polymorphism with risk of nasopharyngeal carcinoma in the central-southern Chinese population.
J. Hum. Genet.
PUBLISHED: 01-16-2014
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This case-control study focused on estimating the association between miR-146a polymorphism and risk of nasopharyngeal carcinoma (NPC) in central-south China. In total, 160 patients with NPC and 200 healthy controls in central-south China were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay. Chi-square test was used to assess the different distribution of miR-146a polymorphism between NPC patients and controls; and logistic regression analysis was applied to analyze the associations between miR-146a polymorphism with cancer risk in different contrast models. Significant differences between NPC patients and controls were found in genotype (P=0.033 for GG versus CG versus CC; and odds ratio (OR)=0.568, 95% confidence interval (CI)=0.354-0.912, P=0.019 for CG versus CC; and OR=0.503, 95% CI=0.261-0.971, P=0.041 for CG versus CC; and OR=0.564, 95% CI=0.360-0.884, P=0.012 for GG+CG versus CC, respectively) and allelic analysis (P=0.025 for G versus C). Our findings suggested that polymorphism of mir-146a was associated with NPC in the central-southern Chinese population.
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Checkpoint kinase 1 is negatively regulated by miR-497 in hepatocellular carcinoma.
Med. Oncol.
PUBLISHED: 01-15-2014
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Checkpoint kinase 1 (CHEK1) is an evolutionarily conserved Ser/Thr kinase, which mediates cell-cycle arrest after DNA damage, and we previously reported that CHEK1 was overexpressed and associated with poor prognosis in hepatocellular carcinoma (HCC), indicating it was oncogenic gene. In this study, we aimed to elucidate the mechanism of CHEK1 overexpression in HCC. We first verified the upregulated CHEK1 by qRT-PCR and western blot in 30 HCC samples compared with corresponding non-tumor liver tissues. In silico analysis showed that CHEK1 was a candidate target of miR-497, which was previously found to be downregulated in HCC by us. To test whether miR-497 could bind to 3'untranslated region (3'UTR) of CHEK1, luciferase reporter assay was conducted. The result revealed that miR-497 could bind to the 3'untranslated region (3'UTR) of CHEK1 mRNA. Western blot showed that ectopic expression of miR-497 suppressed the CHEK1 expression and inhibition of miR-497 led to significant upregulation of CHEK1. Finally, miR-497 expression was measured in the same 30 HCC samples, and the correlation between miR-497 and CHEK1 was analyzed. The results indicated that miR-497 was downregulated in HCC and had a significant negative correlation with CHEK1. Taken together, these results demonstrated that CHEK1 was negatively regulated by miR-497, and the overexpressed CHEK1 was resulted from the downregulated miR-497 in HCC, which provided a potential molecular target for HCC therapy.
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Chemical characteristic and toxicity assessment of particle associated PAHs for the short-term anthropogenic activity event: During the Chinese New Year's Festival in 2013.
Sci. Total Environ.
PUBLISHED: 01-13-2014
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PM10 and PM2.5 samples were simultaneously collected during a period which covered the Chinese New Year's (CNY) Festival. The concentrations of particulate matter (PM) and 16 polycyclic aromatic hydrocarbons (PAHs) were measured. The possible source contributions and toxicity risks were estimated for Festival and non-Festival periods. According to the diagnostic ratios and Multilinear Engine 2 (ME2), three sources were identified and their contributions were calculated: vehicle emission (48.97% for PM10, 53.56% for PM2.5), biomass & coal combustion (36.83% for PM10, 28.76% for PM2.5), and cook emission (22.29% for PM10, 27.23% for PM2.5). An interesting result was found: although the PAHs are not directly from the fireworks display, they were still indirectly influenced by biomass combustion which is affiliated with the fireworks display. Additionally, toxicity risks of different sources were estimated by Multilinear Engine 2-BaP equivalent (ME2-BaPE): vehicle emission (54.01% for PM10, 55.42% for PM2.5), cook emission (25.59% for PM10, 29.05% for PM2.5), and biomass & coal combustion source (20.90% for PM10, 14.28% for PM2.5). It is worth to be noticed that the toxicity contribution of cook emission was considerable in Festival period. The findings can provide useful information to protect the urban human health, as well as develop the effective air control strategies in special short-term anthropogenic activity event.
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Source contributions and spatiotemporal characteristics of PAHs in sediments: Using three-way source apportionment approach.
Environ. Toxicol. Chem.
PUBLISHED: 01-10-2014
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Polycyclic aromatic hydrocarbon (PAHs) were measured in sediments from 29 sites throughout Taihu Lake in China during 2 seasons to investigate spatiotemporal characteristics and source contributions using a 3-way source apportionment approach to positive matrix factorization (PMF3). Seasonal and spatial variations of levels and toxicity suggested higher individual carcinogenic PAH concentrations and toxic equivalent quantity (TEQ) in the flooding season. Three-way PAHs dataset (PAH species, spatial variability, and seasonal variability) was analyzed by PMF3, and its results were compared with a widely used 2-way model (PMF2). Consistent results were observed: vehicular emission was the most important contributor (67.08% by PMF2 and 61.83% by PMF3 for the flooding season; 54.21% by PMF2 and 52.94% by PMF3 for dry season), followed by coal combustion and wood combustion in both seasons. The PMF-cluster analysis was employed to investigate spatial variability of source contributions. Findings can introduce the 3-way approach to apportion sources of PAHs and other persistent organic pollutants (POPs) in sediments, offering the advantage of accounting for information on 3-way datasets.
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Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Case-Control Study and Meta-Analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.
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A promising gene delivery system developed from PEGylated MoS2 nanosheets for gene therapy.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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A new class of two-dimensional (2D) nanomaterial, transition metal dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic physical and chemical properties, has drawn tremendous attention in different fields recently. Herein, we for the first time take advantage of the great potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers for gene delivery and therapy of cancer. In our system, positively charged MoS2-PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and branched polyethylenimine (PEI). The amino end of positively charged nanomaterials can bind to the negatively charged small interfering RNA (siRNA). After detection of physical and chemical characteristics of the nanomaterial, cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was investigated as a well-known oncogene, which was a critical regulator of cell cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA carried by novel nanovector, qPCR and Western blot were used to measure the interfering efficiency; apoptosis assay was used to detect the transfection effect of PLK1. All results showed that the novel nanocarrier revealed good biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability without serum interference, thus would have great potential for gene delivery and therapy.
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Calcium waves initiating from the anomalous subdiffusive calcium sparks.
J R Soc Interface
PUBLISHED: 12-17-2013
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The objective of the study is to investigate the propagation of Ca(2+) waves in full-width cardiac myocytes and carry out sensitivity analysis to study the effects of various physiological parameters on global Ca(2+) waves. Based on the anomalous subdiffusion of Ca(2+) sparks, a mathematical model was proposed to characterize the Ca(2+) waves. The computed results were in agreement with the experimental measurements using confocal microscopy. This model includes variables of current through the Ca(2+) release unit (CRU; ICRU), duration of current flow through CRU (Topen), Ca(2+) sensitivity parameter (K), the longitudinal and transverse spatial separation of CRUs (lx and ly, where x denotes longitudinal direction (x-axis) and y denotes transverse direction (y-axis)) and Ca(2+) diffusion coefficients (Dx, Dy). The spatio-temporal mechanism of the anomalous Ca(2+) sparks led to results that were different from those based on Ficks law. The major findings were reported as: ICRU affected the dynamic properties of Ca(2+) waves more significantly than Topen; the effect of K on the properties of Ca(2+) waves was negligible; ly affected the amplitude significantly, but lx affected the longitudinal velocity significantly; in turn, the limitation and significance of the study are discussed.
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A Regulator of Secretory Vesicle Size, Kelch-Like Protein 12, Facilitates the Secretion of Apolipoprotein B100 and Very-Low-Density Lipoproteins.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 12-12-2013
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One of the major risk factors for atherosclerosis is the plasma level of low-density lipoprotein (LDL), which is a product of very-low-density lipoprotein (VLDL). Hepatic apolipoprotein B100 (apoB100) is the essential component that provides structural stability to VLDL particles. Newly translated apoB100 is partially lipidated in the endoplasmic reticulum (ER), forming nascent apoB100-VLDL particles. These particles are further modified to form fully mature VLDLs in the Golgi apparatus. Therefore, the transport of nascent VLDL from the ER to the Golgi represents a critical step during VLDL maturation and secretion and in regulating serum LDL cholesterol levels. Our previous studies showed that apoB100 exits the ER in coat complex II vesicles, but the cohort of related factors that control trafficking is poorly defined.
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Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients: a multicenter, open-label, phase III study.
HBPD INT
PUBLISHED: 12-11-2013
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Contrast agents help to improve visibility in magnetic resonance (MR) imaging. However, owing to the large interstitial spaces of the liver, there is a reduction in the natural contrast gradient between lesions and healthy tissue. This study was undertaken to evaluate the efficacy and safety of the liver-specific MR imaging contrast agent gadoxetate disodium (Gd-EOB-DTPA) in Chinese patients.
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Association Between Seven Common OPG Genetic Polymorphisms and Osteoporosis Risk: A Meta-Analysis.
DNA Cell Biol.
PUBLISHED: 11-27-2013
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Functional polymorphisms of the osteoprotegerin (OPG) gene are known to be involved in bone mineral density and the development of osteoporosis; however, some conflicting results have been reported. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the relationship between seven common OPG genetic polymorphisms (T149C, A163G, G209A, T245G, T950C, G1181C, and C1217T) and osteoporosis risk. A literature search for eligible studies published before August 1st, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI (China National Knowledge Infrastructure) databases. Pooled odds ratios and their corresponding 95% confidence intervals were used to evaluate the strength of the association under fixed- or random-effect models according to a heterogeneity test. All analyses were performed using the STATA software, version 12.0. Fourteen case-control studies with a total of 2383 osteoporosis cases and 2280 healthy controls were included in this meta-analysis. Among the seven polymorphisms, A163G and G1181C revealed significant associations with osteoporosis risk. For A163G (rs3102735), the combined results showed that the G allele of the A163G polymorphism may be associated with an increased risk of osteoporosis. Stratified analyses showed that the magnitude of the effect was similar in Caucasian and postmenopausal woman subgroups. For G1181C (rs2073618), however, we found that individuals with the C allele of the G1181C polymorphism had a decreased risk of osteoporosis, especially in Asian and postmenopausal woman subgroups. In summary, this meta-analysis indicated that the G allele of the OPG A163G polymorphism might increase osteoporosis risk in Caucasians, whereas individuals with the C allele of the G1181C polymorphism had a decreased risk of osteoporosis, especially in Asians. Both of these effects were observed in postmenopausal women. These polymorphisms could probably be used with other genetic markers together to identify individuals at a high risk of osteoporosis.
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Nucleotide-induced asymmetry within ATPase activator ring drives ?54-RNAP interaction and ATP hydrolysis.
Genes Dev.
PUBLISHED: 11-19-2013
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It is largely unknown how the typical homomeric ring geometry of ATPases associated with various cellular activities enables them to perform mechanical work. Small-angle solution X-ray scattering, crystallography, and electron microscopy (EM) reconstructions revealed that partial ATP occupancy caused the heptameric closed ring of the bacterial enhancer-binding protein (bEBP) NtrC1 to rearrange into a hexameric split ring of striking asymmetry. The highly conserved and functionally crucial GAFTGA loops responsible for interacting with ?54-RNA polymerase formed a spiral staircase. We propose that splitting of the ensemble directs ATP hydrolysis within the oligomer, and the rings asymmetry guides interaction between ATPase and the complex of ?54 and promoter DNA. Similarity between the structure of the transcriptional activator NtrC1 and those of distantly related helicases Rho and E1 reveals a general mechanism in homomeric ATPases whereby complex allostery within the ring geometry forms asymmetric functional states that allow these biological motors to exert directional forces on their target macromolecules.
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Synthesis of Au-Fe3O4 heterostructured nanoparticles for in vivo computed tomography and magnetic resonance dual model imaging.
Nanoscale
PUBLISHED: 11-18-2013
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Water-soluble Au-Fe3O4 heterostructured nanoparticles with high biocompatibility were synthesized and applied as a dual modality contrast agent. These nanoparticles present strong CT/MRI contrast enhancement in a rabbit model. Low concentrations of Au-Fe3O4 were found to obtain a similar effect to high concentrations of a commercial iodine agent in the CT image.
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Association Between Pre-hypertension and Cardiovascular Outcomes: A Systematic Review and Meta-analysis of Prospective Studies.
Curr. Hypertens. Rep.
PUBLISHED: 11-16-2013
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The quantitative associations between prehypertension or its separate blood pressure (BP) ranges and the risk of main cardiovascular diseases (CVDs) have not been reliably documented.
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p300-Dependent Acetylation of ATF5 Enhances C/EBP? Transactivation of C/EBP? During 3T3-L1 Differentiation.
Mol. Cell. Biol.
PUBLISHED: 11-11-2013
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Adipogenesis is a multistep process by which 3T3-L1 preadipocytes differentiate into mature adipocytes through mitotic clonal expansion (MCE) and terminal differentiation. The CCAAT/enhancer-binding protein (C/EBP) ? is an important transcription factor that takes part in both of these processes. C/EBP? not only transactivates C/EBP? and the peroxisome proliferator-activated receptor (PPAR) ?, which cause 3T3-L1 preadipocytes to enter terminal adipocyte differentiation, but is also required to activate cell cycle genes necessary for MCE. The identification of potential cofactors of C/EBP? will help to explain how C/EBP? undertakes these specialized roles during the different stages of adipogenesis. In this study, we found that activating transcription factor 5 (ATF5) can bind to the promoter of C/EBP? via its direct interaction with C/EBP? (which is mediated via the p300-dependent acetylation of ATF5) leading to enhanced C/EBP? transactivation of C/EBP?. We also show that p300 is important for the interaction of ATF5 with C/EBP? as well as the binding activity of this complex on the C/EBP? promoter. Consistent with these findings, overexpression of ATF5 and an acetylated ATF5 mimic both promoted 3T3-L1 adipocyte differentiation, whereas siRNA-mediated ATF5 down-regulation inhibited this process. Furthermore, we show that the elevated expression of ATF5 is correlated with an obese phenotype in both mice and humans. In summary, we have identified ATF5 as a new cofactor of C/EBP? and examined how C/EBP? and ATF5 (acetylated by a p300-dependent mechanism) regulate the transcription of C/EBP?.
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Magnetic PEGylated Pt3Co nanoparticles as a novel MR contrast agent: in vivo MR imaging and long-term toxicity study.
Nanoscale
PUBLISHED: 10-30-2013
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Magnetic resonance (MR) imaging using magnetic nanoparticles as the contrast agent has been extensively explored in biomedical imaging and disease diagnosis. Herein, we develop biocompatible polymer coated ultra-small Pt3Co magnetic nanoparticles as a new T2-weighted MR imaging contrast agent. A unique class of alloy Pt3Co nanoparticles is synthesized through a thermal decomposition method. After being modified with polyethylene glycol (PEG), the obtained Pt3Co-PEG nanoparticles exhibit an extremely high T2-weighted relaxivity rate (r2) up to 451.2 mM s(-1), which is much higher than that of Resovist®, a commercial T2-MR contrast agent used in the clinic. In vitro experiments indicate no obvious cytotoxicity of Pt3Co-PEG nanoparticles to various cell lines. After intravenous injection of Pt3Co-PEG nanoparticles, in vivo T2-weighted MR imaging of tumor-bearing mice reveals strong tumor contrast, which is much higher than that offered by injecting Resovist®. We further study the long-term biodistribution and toxicology of this new type of MR contrast nanoparticles after intravenous injection into healthy mice. Despite the significant retention of Pt3Co-PEG nanoparticles in the mouse liver and spleen, no appreciable toxicity of these nanoparticles to the treated animals has been noted in our detailed histological and hematological analysis over a course of 60 days. Our work demonstrates that functionalized Pt3Co nanoparticles may be a promising new type of T2-weighted MR contrast agent potentially useful in biomedical imaging and diagnosis.
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Hypospadias and residential proximity to pesticide applications.
Pediatrics
PUBLISHED: 10-28-2013
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Experimental evidence suggests pesticides may be associated with hypospadias.
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Docosahexaenoic acid impairs the maturation of very low density lipoproteins in rat hepatic cells.
J. Lipid Res.
PUBLISHED: 10-17-2013
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One mechanism of the lipid-lowering effects of the fish oil n-3 fatty acids [e.g., docosahexaenoic acid (DHA)] in cell and animal models is induced hepatic apolipoprotein B100 (apoB) presecretory degradation. This degradation occurs post-endoplasmic reticulum, but whether DHA induces it before or after intracellular VLDL formation remains unanswered. We found in McA-RH7777 rat hepatic cells that DHA and oleic acid (OA) treatments allowed formation of pre-VLDL particles and their transport to the Golgi, but, in contrast to OA, with DHA pre-VLDL particles failed to quantitatively assemble into fully lipidated (mature) VLDL. This failure required lipid peroxidation and was accompanied by the formation of apoB aggregates (known to be degraded by autophagy). Preventing the exit of proteins from the Golgi blocked the aggregation of apoB but did not restore VLDL maturation, indicating that failure to fully lipidate apoB preceded its aggregation. ApoB autophagic degradation did not appear to require an intermediate step of cytosolic aggresome formation. Taken with other examples in the literature, the results of this study suggest that pre-VLDL particles that are competent to escape endoplasmic reticulum quality control mechanisms but fail to mature in the Golgi remain subject to quality control surveillance late in the secretory pathway.
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Multilayer dual-polymer-coated upconversion nanoparticles for multimodal imaging and serum-enhanced gene delivery.
ACS Appl Mater Interfaces
PUBLISHED: 10-10-2013
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Upconversion nanoparticles (UCNPs) have been widely explored for various bioapplications because of their unique optical properties, easy surface functionalization, and low cytotoxicity. Herein, we synthesize gadolinium (Gd3+)-doped UCNPs, which are modified first with poly(ethylene glycol) (PEG) and then with two layers of poly(ethylenimine) (PEI) via covalent conjugation and layer-by-layer assembly, respectively. Compared with UCNP-PEG@1×PEI with only one layer of PEI coating, the final complex, UCNP-PEG@2×PEI, with two PEI layers exhibits reduced cytotoxicity and enhanced gene transfection efficiency. It is interesting to find that while free PEI polymer is only effective in gene transfection in a serum-free medium and shows drastically reduced transfection ability if serum is added, UCNP-PEG@2×PEI is able to transfect cells in both serum-free and -containing media and, surprisingly, offers even higher gene transfection efficiency if serum is added. This is likely due to the formation of protein corona on the nanoparticle surface, which triggers the receptor-mediated endocytosis of our UCNP vectors. Considering the upconversion luminescence and magnetic resonance imaging contrasting ability of UCNPs, our novel nanovector could serve as a "trackable" gene-delivery carrier promising for theranostic applications.
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Deconvolving the temporal response of photoelectric x-ray detectors for the diagnosis of pulsed radiations.
Rev Sci Instrum
PUBLISHED: 10-05-2013
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Based on the conjugate gradient method, a simple algorithm is presented for deconvolving the temporal response of photoelectric x-ray detectors (XRDs) to reconstruct the resolved time-dependent x-ray fluxes. With this algorithm, we have studied the impact of temporal response of XRD on the radiation diagnosis of hohlraum heated by a short intense laser pulse. It is found that the limiting temporal response of XRD not only postpones the rising edge and peak position of x-ray pulses but also smoothes the possible fluctuations of radiation fluxes. Without a proper consideration of the temporal response of XRD, the measured radiation flux can be largely misinterpreted for radiation pulses of a hohlraum heated by short or shaped laser pulses.
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Protein inhibitor of activated STAT 1 (PIAS1) is identified as the SUMO E3 ligase of CCAAT/enhancer-binding protein ? (C/EBP?) during adipogenesis.
Mol. Cell. Biol.
PUBLISHED: 09-23-2013
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It is well recognized that PIAS1, a SUMO (small ubiquitin-like modifier) E3 ligase, modulates such cellular processes as cell proliferation, DNA damage responses, and inflammation responses. Recent studies have shown that PIAS1 also plays a part in cell differentiation. However, the role of PIAS1 in adipocyte differentiation remains unknown. CCAAT/enhancer-binding protein ? (C/EBP?), a major regulator of adipogenesis, is a target of SUMOylation, but the E3 ligase responsible for the SUMOylation of C/EBP? has not been identified. The present study showed that PIAS1 functions as a SUMO E3 ligase of C/EBP? to regulate adipogenesis. PIAS1 expression was significantly and transiently induced on day 4 of 3T3-L1 adipocyte differentiation, when C/EBP? began to decline. PIAS1 was found to interact with C/EBP? through the SAP (scaffold attachment factor A/B/acinus/PIAS) domain and SUMOylate it, leading to increased ubiquitination and degradation of C/EBP?. C/EBP? became more stable when PIAS1 was silenced by RNA interference (RNAi). Moreover, adipogenesis was inhibited by overexpression of wild-type PIAS1 and promoted by knockdown of PIAS1. The mutational study indicated that the catalytic activity of SUMO E3 ligase was required for PIAS1 to restrain adipogenesis. Importantly, the inhibitory effect of PIAS1 overexpression on adipogenesis was rescued by overexpressed C/EBP?. Thus, PIAS1 could play a dynamic role in adipogenesis by promoting the SUMOylation of C/EBP?.
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Refining the Human iPSC-Cardiomyocyte Arrhythmic Risk Assessment Model.
Toxicol. Sci.
PUBLISHED: 09-19-2013
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Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are capable of detecting drug-induced clinical arrhythmia, Torsade de Pointes (TdP), and QT prolongation. Efforts herein employ a broad set of structurally diverse drugs to optimize the predictive algorithm for applications in discovery toxicology and cardiac safety screening. The changes in the beat rhythm and rate of a confluent monolayer of hiPS-CMs by 88 marketed and 30 internal discovery compounds were detected with real-time cellular impedance measurement and quantified by measures of arrhythmic beating (IB20, lowest concentration inducing ? 20% arrhythmic [irregular, atypical] beats in 3 consecutive 20-s sweeps, and predicted proarrhythmic score [PPS]-IB20) or changes in beat rate (BR20, the lowest concentration inducing a reduction in beat rate of ? 20% at 3 consecutive sweeps compared with the time-matched vehicle control group, and PPS-BR20). Drug-induced arrhythmic beats and reductions in beat rates are predictive of clinical arrhythmia and QT prolongation, respectively. A threshold of ? 10?M for class determination results in 82% in vitro-in vivo concordance for TdP prediction and 91% sensitivity for non-TdP arrhythmia detection, or 83% and 91% if clinically efficacious plasma (effective serum therapeutic concentration [C eff]) values are incorporated. This human cardiomyocyte arrhythmic risk (hCAR) model provides greater predictivity for torsadogenicity in humans compared with either human ether-a-go-go-related gene (hERG) inhibition (75%) or QT prolongation (81%). The concordance of beat rate reductions to predict clinical QT prolongation is 86%, or 87% when C eff is considered, which is greater than a hERG signal (80%). Further, arrhythmic beats resulting from cytotoxicity were identified by a distinct arrhythmic beating pattern, which occurred after the onset of cytolethality. This hCAR assay showed increased performance over existing preclinical tools in predicting clinical QT prolongation, arrhythmia, and TdP. Thus, hiPS-CMs are a relevant cell system to improve evaluating cardiac safety liabilities of drug candidates.
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Adsorption characteristics of Cu and Zn onto various size fractions of aggregates from red paddy soil.
J. Hazard. Mater.
PUBLISHED: 09-02-2013
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Soil aggregate is the basic structure unit of soils and the ability of various size fractions are different in the aspect of adsorbing and transferring heavy metals in the environment. In this study, bulk soil from red paddy field was partitioned into four aggregate-size fractions and their adsorption characteristics for Cu and Zn were studied. Our results showed that: Pseudo-second order model was more successful to fit the adsorption process in the kinetic experiments and the isothermal experiments data can be described well with the Freundlich model as a whole. Due to higher contents in organic matter, CEC and free iron oxide, the <0.002mm fraction was found to have the highest initial sorption rate and maximum adsorption capacity. The adsorption amount of metals increased as the increasing of pH and the percentage of adsorbed metal susceptible to desorption into 0.01M NaNO3 was greater for Zn than for Cu, while their variation trends were quite opposite. More specific adsorption sites in the <0.002mm fraction lead to more desorption amount for this particle size of soil at low pH condition. After 60 days of incubation, Cu and Zn were observed to enrich in the clay-size aggregates with fractions more stable than other particles.
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Stretchable Polymeric Multielectrode Array for Conformal Neural Interfacing.
Adv. Mater. Weinheim
PUBLISHED: 08-16-2013
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A highly stretchable neural interface of concurrent robust electrical and mechanical properties is developed with a conducting polymer film as the sole conductor for both electrodes and leads. This neural interface offers the benefits of conducting polymer electrodes in a demanding stretchable format, including low electrode impedance and high charge-injection capacity, due to large electroactive surface area of the electrode.
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The mystery of missing female children in the Caucasus: an analysis of sex ratios by birth order.
Int Perspect Sex Reprod Health
PUBLISHED: 07-31-2013
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Official data on sex ratios at birth suggest a rise in sex-selective abortions in some post-Soviet states following the introduction of ultrasonography. However, questions remain about the validity of official data in these nations as well as whether the high sex ratios at birth are a statistical artifact.
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Historical trends of concentrations, source contributions and toxicities for PAHs in dated sediment cores from five lakes in western China.
Sci. Total Environ.
PUBLISHED: 07-24-2013
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In this work, sixteen U.S. EPA priority PAH compounds in the dated sediment cores were detected from five lakes in western China. In most lakes, the concentrations of the total PAHs (?PAHs) increased from the deep layers to the surface sediments. Two source categories, i.e. vehicular emission and biomass & domestic coal combustion were identified by Unmix, a factor analysis receptor model to explore the source contributions of PAHs in the dated sediments. The source apportionment results showed that biomass & domestic coal combustion contributed larger proportion of PAHs in the five lakes. The toxicities of PAHs in the dated sediments, assessed by BaP equivalent (BaPE) values showed that the BaPE increased gradually from the deep layers to the surface sediments in most lakes. For the first effort, the contribution of each source to BaPE was apportioned by Unmix-BaPE method, and the result indicated that the vehicular emission posed the highest toxic risk. The percentage contribution of vehicular emission for PAHs and BaPE also increased from the deep layers to the surface sediments, while biomass & domestic coal combustion exhibited the opposite tendency.
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[Late-onset hypogonadism among old and middle-aged males in a rural community of Zhejiang Province].
Zhonghua Nan Ke Xue
PUBLISHED: 07-19-2013
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To investigate the epidemiology of late-onset hypogonadism (LOH) in old and middle-aged males in the rural area of Southern China.
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Role of Angptl4 in vascular permeability and inflammation.
Inflamm. Res.
PUBLISHED: 07-01-2013
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Angptl4 is a secreted protein involved in the regulation of vascular permeability, angiogenesis, and inflammatory responses in different kinds of tissues. Increases of vascular permeability and abnormality changes in angiogenesis contribute to the pathogenesis of tumor metastasis, ischemic-reperfusion injury. Inflammatory response associated with Angptl4 also leads to minimal change glomerulonephritis, wound healing. However, the role of Angptl4 in vascular permeability, angiogenesis, and inflammation is controversy. Hence, an underlying mechanism of Angptl4 in different kind of tissues needs to be further clarified.
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Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma.
Clin. Cancer Res.
PUBLISHED: 06-28-2013
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MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma and delineate their clinical significance for hepatocellular carcinoma.
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Effect of dexmedetomidine on lung ischemia?reperfusion injury.
Mol Med Rep
PUBLISHED: 06-24-2013
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Dexmedetomidine, a specific selective ?2?adrenergic agonist, does not only have the characteristics of being a sedative and analgesic, but also exhibits a protective role in brain ischemia?reperfusion injury and inhibits the inflammation in animals with sepsis. The objective of the present study was to investigate whether dexmedetomidine is capable of attenuating rat pulmonary damage induced by ischemia?reperfusion injury, which is a type of acute sterile lung injury. Sprague?Dawley rats were randomly assigned into six groups: The sham?operated (sham) group, the lung ischemia?reperfusion (I/R) group, intravenous injection of dexmedetomidine 2.5 µg/kg/h (Dex2.5) or 5 µg/kg/h (Dex5) for 1 h prior to ischemia, combination of ?2?adrenergic antagonist yohimbine prior to dexmedetomidine pre?treatment (Dex+Yoh) and pre?administration of yohimbine alone (Yoh) prior to ischemia. Lung injury was assessed by the histopathological changes, arterial blood gas, wet/dry (w/d) weight ratio and myeloperoxidase (MPO) activity of the lung. The concentration of tumor necrosis factor?? (TNF??), interleukin?6 (IL?6) and monocyte chemoattractant protein?1 (MCP?1) in bronchoalveolar lavage fluid (BALF) was measured by an enzyme-linked immunosorbent assay. The expression of toll?like receptor?4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA in the lung were determined by quantitative PCR, and phosphorylated levels of c?Jun N?terminal kinase (JNK) and extracellular signal?regulated kinase (ERK)1/2 were determined by western blotting. Pre?treatment with dexmedetomidine significantly reduced the lung injury, w/d weight ratio and MPO activity, and decreased the concentration of TNF??, IL?6 and MCP?1 in BALF compared with the I/R group. The expression of TLR4 and MyD88 mRNA and the levels of phosphorylated JNK and ERK1/2 in the lung tissue were markedly downregulated by intravenous injection of dexmedetomidne for 1 h prior to lung I/R. The protective effects of dexmedetomidine on the lung were not completely reversed by the ?2?adrenergic antagonist, yohimbine. Pre?treatment with dexmedetomidine is capable of reducing pulmonary damage and inhibiting sterile inflammation induced by lung I/R injury. TLR4/MyD88/mitogen-activated protein kinase (MAPK) signaling is involved in the protective mechanism of dexmedetomidine through ?2?adrenoceptor independence.
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[Feasibility of the aging males symptoms scale for the male population of Shanghai].
Zhonghua Nan Ke Xue
PUBLISHED: 06-14-2013
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To assess the reliability and validity of the Aging Males Symptoms (AMS) scale in the male population of Shanghai.
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Transactivation of Atg4b by C/EBP? promotes autophagy to facilitate adipogenesis.
Mol. Cell. Biol.
PUBLISHED: 06-10-2013
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Autophagy is a highly conserved self-digestion pathway involved in various physiological and pathophysiological processes. Recent studies have implicated a pivotal role of autophagy in adipocyte differentiation, but the molecular mechanism for its role and how it is regulated during this process are not clear. Here, we show that CCAAT /enhancer-binding protein ? (C/EBP?), an important adipogenic factor, is required for the activation of autophagy during 3T3-L1 adipocyte differentiation. An autophagy-related gene, Atg4b, is identified as a de novo target gene of C/EBP? and is shown to play an important role in 3T3-L1 adipocyte differentiation. Furthermore, autophagy is required for the degradation of Klf2 and Klf3, two negative regulators of adipocyte differentiation, which is mediated by the adaptor protein p62/SQSTM1. Importantly, the regulation of autophagy by C/EBP? and the role of autophagy in Klf2/3 degradation and in adipogenesis are further confirmed in mouse models. Our data describe a novel function of C/EBP? in regulating autophagy and reveal the mechanism of autophagy during adipocyte differentiation. These new insights into the molecular mechanism of adipose tissue development provide a functional pathway with therapeutic potential against obesity and its related metabolic disorders.
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