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Find video protocols related to scientific articles indexed in Pubmed.
Specific Gene Repression by CRISPRi System Transferred through Bacterial Conjugation.
ACS Synth Biol
PUBLISHED: 11-20-2014
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In microbial communities, bacterial populations are commonly controlled using indiscriminate, broad range antibiotics. There are few ways to target specific strains effectively without disrupting the entire microbiome and local environment. Here we use conjugation, a natural DNA horizontal transfer process among bacterial species, to deliver an engineered CRISPR interference (CRISPRi) system for targeting specific genes in recipient Escherichia coli cells. We show that delivery of the CRISPRi system is successful and can specifically repress a reporter gene in recipient cells, thereby establishing a new tool for gene regulation across bacterial cells and potentially for bacterial population control.
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A Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles.
J. Med. Chem.
PUBLISHED: 11-20-2014
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Gatekeeper T790M mutation in EGFR is the most prevalent factor underlying acquired resistance. Acrylamide-bearing quinazoline derivatives are powerful irreversible inhibitors for overcoming resistance. Nevertheless, concerns about the risk of non-specific covalent modification have motivated the development of novel cysteine-targeting inhibitors. In this paper, we demonstrate that fluoro-substituted olefins can be tuned to alter Michael addition reactivity. Incorporation of these olefins into the quinazoline templates produced potent EGFR inhibitors with improved safety and pharmacokinetic properties. A lead compound 5a was validated against EGFRWT, EGFR T790M as well as A431 and H1975 cancer cell lines. Additionally, compound 5a displayed a weaker inhibition against the EGFR-independent cancer cell line SW620 when compared withafatinib. Oral administration of 5a at a dose of 30mg/kg induced tumor regression in a murine-EGFRL858R/T790M driven H1975 xenograft model. Also, 5a exhibited improved oral bioavailability and safety, as well as favorable tissue distribution properties and enhanced brain uptake. These findings provide the basis of a promising strategy toward the treatment of NSCLC patients with drug resistance.
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Plasma-induced grafting of polyacrylamide on graphene oxide nanosheets for simultaneous removal of radionuclides.
Phys Chem Chem Phys
PUBLISHED: 11-20-2014
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Polyacrylamide (PAM) grafted graphene oxide (denoted as PAM/GO) was synthesized by the plasma-induced polymerization technique and applied as an adsorbent for the simultaneous removal of radionuclides from radioactive wastewater. The interactions of PAM/GO with the radionuclides U(vi), Eu(iii) and Co(ii) were studied, along with their sorption kinetics. The results indicated that radionuclide sorption on PAM/GO was affected by the solution pH and ionic strength. The maximum sorption capacities of U(vi), Eu(iii) and Co(ii) on PAM/GO (0.698, 1.245 and 1.621 mmol g(-1), respectively) at pH = 5.0 ± 0.1 and T = 295 K were much higher than those of radionuclides on GO and other adsorbents. The thermodynamic data (?H(0), ?S(0) and ?G(0)) calculated from the temperature-dependent sorption isotherms suggested that the sorption of radionuclides on PAM/GO was a spontaneous and endothermic process. These results indicate that PAM/GO is a promising material for the control of radionuclide pollution.
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A structural atlas of kinases inhibited by clinically approved drugs.
Meth. Enzymol.
PUBLISHED: 11-18-2014
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The aberrant activation of protein kinases is associated with many human diseases, most notably cancer. Due to this link between kinase deregulation and disease progression, kinases are one of the most targeted protein families for small-molecule inhibition. Within the last 15 years, the U.S. Food and Drug Administration has approved over 20 small-molecule inhibitors of protein kinases for use in the clinic. These inhibitors target the kinase active site and represent the successful hurdling by medicinal chemists of the formidable challenge posed by the high similarity among the active sites of the approximately 500 human kinases. We review the conserved structural features of kinases that are important for inhibitor binding as well as for catalysis. Many clinically approved drugs elicit selectivity by exploiting subtle variation within the kinase active site. We highlight some of the crystallographic studies on the kinase-inhibitor complexes that have provided valuable guidance for the development of these drugs as well as for future drug design efforts.
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Helminth.net: expansions to Nematode.net and an introduction to Trematode.net.
Nucleic Acids Res.
PUBLISHED: 11-14-2014
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Helminth.net (http://www.helminth.net) is the new moniker for a collection of databases: Nematode.net and Trematode.net. Within this collection we provide services and resources for parasitic roundworms (nematodes) and flatworms (trematodes), collectively known as helminths. For over a decade we have provided resources for studying nematodes via our veteran site Nematode.net (http://nematode.net). In this article, (i) we provide an update on the expansions of Nematode.net that hosts omics data from 84 species and provides advanced search tools to the broad scientific community so that data can be mined in a useful and user-friendly manner and (ii) we introduce Trematode.net, a site dedicated to the dissemination of data from flukes, flatworm parasites of the class Trematoda, phylum Platyhelminthes. Trematode.net is an independent component of Helminth.net and currently hosts data from 16 species, with information ranging from genomic, functional genomic data, enzymatic pathway utilization to microbiome changes associated with helminth infections. The databases' interface, with a sophisticated query engine as a backbone, is intended to allow users to search for multi-factorial combinations of species' omics properties. This report describes updates to Nematode.net since its last description in NAR, 2012, and also introduces and presents its new sibling site, Trematode.net.
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[Effects of carotid endarterectomy on cognitive function in patients with carotid stenosis].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 11-06-2014
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To investigate the theraputic effects of carotid endarterectomy (CEA) on cognitive function in patients with carotid stenosis (CAS) and congnitive impairment.
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Redox-switchable host-guest systems based on a bisthiotetrathiafulvalene-bridged cryptand.
Chem. Commun. (Camb.)
PUBLISHED: 10-31-2014
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By attaching a bisthiotetrathiafulvalene (STTFS) unit to the third arm of the cryptand, a redox-switchable bis(m-phenylene)-32-crown-10-based cryptand was synthesized successfully. It was found that the dethreading-rethreading processes between this cryptand and the guests could be well-controlled in different redox states owing to the specific redox-active properties of the STTFS unit.
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[Intervention of NGAL and HO-1 in valve replacement surgery-induced acute kidney injury].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-31-2014
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To determine the pathological mechanism and prevent heart-renal syndrome after heart valve replacement surgery.
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Chitinophaga qingshengii sp. nov., isolated from weathered rock surface.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 10-25-2014
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A novel type of mineral-weathering bacterium was isolated from weathered rock (potassic trachyte) surfaces collected from Nanjing (Jiangsu, China). Cells of strain JN246T were Gram-stain-negative, rod-shaped, and non-motile. Strain JN246T was aerobic, catalase- and oxidase-positive, and grew optimally at 28 °C and pH 7.0. On the basis of 16S rRNA gene sequence analysis, strain JN246T belonged to the genus Chitinophaga and the closest phylogenetic relatives were Chitinophaga eiseniae YC6729T (98.5 %), Chitinophaga terrae KP01T (96.8 %), and Chitinophaga jiangningensis JN53T (96.3 %). The major respiratory quinine was MK-7 and the major polyamine was homospermidine. The major fatty acids were iso-C15:0, C16:1?5c, C16:0, iso-C17:0 3-OH, iso-C15:0 3-OH, C14:O, C16:0 3-OH, C16:1?7c and/or C16:1?6c (summed feature 3), and C13:1. The polar lipid profile of strain JN246T consisted of phosphatidylethanolamine, unknown aminolipids and unknown lipids. The genomic DNA G + C content of strain JN246T was 48.8 mol%. Based on the low level of DNA-DNA relatedness (ranging from 22.6 % to 42.4 %) to these type strains of species of the genus Chitinophaga and unique phenotypic characteristics, strain JN246T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga qingshengii sp. nov. is proposed. The type strain is JN246T (= CCTCC AB 2014201 T= JCM 30026 T).
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[Catheter aspiration alone or combined with thrombolysis in the treatment of superior mesenteric artery embolism].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 10-25-2014
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To investigate the efficacy of catheter aspiration or combined with thrombolysis in the treatment of superior mesenteric artery embolism(SMAE).
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[Establishment and biological characteristics of a platinum-resistance nude mouse model in epithelial ovarian cancer].
Zhonghua Fu Chan Ke Za Zhi
PUBLISHED: 10-21-2014
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To establish a platinum resistance nude mice model of epithelial ovarian cancer (EOC) and investigate its resistance to cisplatin (DDP) biological characteristics, so as to provide evidences for exploring chemoresistence mechanisms and screening for reversal targets in vivo micro-environment.
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Spontaneous emission modulation of colloidal quantum dots via efficient coupling with hybrid plasmonic photonic crystal.
Opt Express
PUBLISHED: 10-17-2014
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The spontaneous emission of colloidal CdSe/ZnS quantum dots (CQDs) modified by the hybrid plasmonic-photonic crystal is reported in this paper. By using a spin coater, the spatial overlap between CQDs and the surface resonance modes in this quasi-2D crystal slab is achieved. In this case, the coupling efficiency of them is enhanced greatly and most excited CQDs radiate through the surface modes. Consequently, despite the low refractive index contrast of our hybrid structure, the directionality of spontaneous emission, increased radiative probability and narrowed full width at half maximum of emission peak are all clearly observed by our home-made microscopic angle-resolved spectroscopy and time-resolved photoluminescence system. Our results manifest that the quasi-2D hybrid plasmonic-photonic crystal is an ideal candidate to tailor the radiative properties of CdSe/ZnS CQDs, which might be significant for the applications of light emitting devices.
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The Difference Between Slow and Forced Vital Capacity Increases With Increasing Body Mass Index: A Paradoxical Difference in Low and Normal Body Mass Indices.
Respir Care
PUBLISHED: 10-16-2014
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Obesity reduces FVC, the most commonly used measurement of vital capacity (VC) and slow VC (SVC). It is unknown whether the difference between SVC and FVC is constant in different body mass indices (BMIs). We hypothesized that the difference between SVC and FVC increases as a function of BMI.
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Synthesis of brassinosteroids analogues from laxogenin and their plant growth promotion.
Nat. Prod. Res.
PUBLISHED: 10-14-2014
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Four steroid saponins (2-5) and three derivatives (6-8) were synthesised from laxogenin. Four of them were new compounds: (25R)-3?-(2,3,4,6-tetra-O-acetyl-?-d-galactopyranosyloxy)-5?-spirostan-6-one (3), (25R)-3?-(?-d-galactopyranosyloxy)-5?-spirostan-6-one (5), 3?,16-diacetyl-26-hydroxy-5?-cholestan-6,22-dione (6) and 16-acetyl-3?,26-dihydroxy-5?-cholestan-6,22-dione (7). All the compounds showed plant growth-promoting activity in the radish hypocotyl elongation and cotyledon expansion bioassay. Above all, 2 and 6 were found to be more active.
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NS5ATP9 Suppresses Activation of Human Hepatic Stellate Cells, Possibly via Inhibition of Smad3/Phosphorylated-Smad3 Expression.
Inflammation
PUBLISHED: 10-11-2014
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Activation of hepatic stellate cell (HSC) is the central event in liver fibrosis. NS5ATP9 is related to many malignant tumors, but little is known about its function in HSC activation. The aim of this study is to investigate the role of NS5ATP9 in HSC activation in vitro. Genes related to liver fibrosis were detected after NS5ATP9 overexpression or silencing with or without transforming growth factor (TGF)-?1 stimulation in the human HSCs by real-time polymerase chain reaction and western blotting. Cell proliferation, migration, and apoptosis were tested, and the mechanisms underlying the effect of NS5ATP9 on HSC activation were studied. We showed that NS5ATP9 suppressed HSC activation and collagen production, with or without TGF-?1 induction. Also, NS5ATP9 inhibited cell proliferation and migration and promoted apoptosis. Furthermore, NS5ATP9 reduced basal and TGF-?1-mediated Smad3/phosphorylated-Smad3 expression. The existence of a physical complex between NS5ATP9 and Smad3 was illustrated. NS5ATP9 suppresses HSC activation, extracellular matrix production, and promotes apoptosis, in part through reducing Smad3/phosphorylated-Smad3 expression.
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Retention of Homeless Smokers in the Power to Quit study.
Nicotine Tob. Res.
PUBLISHED: 10-09-2014
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Concerns about retention are a major barrier to conducting studies enrolling homeless individuals. Since smoking is a major problem in homeless communities and research on effective methods of promoting smoking cessation is needed, we describe strategies used to increase retention and participant characteristics associated with retention in smoking cessation study enrolling homeless adults.
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Oat ?-glucan: physico-chemical characteristics in relation to its blood-glucose and cholesterol-lowering properties.
Br. J. Nutr.
PUBLISHED: 10-01-2014
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The water-soluble, mixed-linkage ?-glucan, a form of soluble dietary fibre, is considered the main biologically active component responsible for the capacity of many oat products to lower postprandial glycaemia and fasting plasma cholesterol in human subjects. The present review discusses the physical and chemical properties of oat ?-glucan that are considered important predictors of these beneficial metabolic effects. In vitro modelling and animal and human studies have provided compelling evidence showing that the ability of oat ?-glucan to increase the viscosity of digesta in the gastrointestinal tract (GIT) is a primary determinant of its blood-glucose and cholesterol-lowering properties. Therefore, the chemical structure, molecular weight (MW), the rate and extent of dissolution and solution rheology of oat ?-glucan are key factors in determining the physiological function of oat-containing foods. The structure and properties of oat ?-glucan vary between species and varieties of oats, and are also affected by the growing and storage conditions and processing of oat grain. In addition, the extraction and analysis methods may also contribute to the variations in the structure, MW, hydration and solution rheology of ?-glucan obtained from different laboratories. Recent work has demonstrated that ?-glucan solubility in foods depends on the source of the material and processing conditions; solubility may also be subject to changes during food preparation and storage (such as freezing). In conclusion, both the amount and MW of ?-glucan that are solubilised in the GIT need to be considered when assessing the blood-glucose and cholesterol-lowering properties of oat-containing foods.
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Clinical characteristics of human infection with a novel avian-origin influenza A(H10N8) virus.
Chin. Med. J.
PUBLISHED: 10-01-2014
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Novel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A (H10N8) virus which can infect humans and cause severe diseases.
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[Single-molecule detection and characterization of DNA replication based on DNA origami].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-30-2014
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To investigate single-molecule detection and characterization of DNA replication.
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Low-SES Children's Eyewitness Memory: The Effects of Verbal Labels and Vocabulary Skills.
Behav Sci Law
PUBLISHED: 09-28-2014
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This study examined the effects of the verbal labels procedure and vocabulary skills on low-socioeconomic status (SES) preschool children's eyewitness memory. Children (N =176) aged 3-5 years witnessed a conflict event and were then questioned about it in either a standard or a verbal labels interview. Findings revealed that children with higher rather than lower vocabulary skills produced more complete and accurate memories. Children who were given the verbal labels interview recalled more information, which included both correct and incorrect details. Overall, the verbal labels procedure did not improve children's performance on direct questions, but children with low vocabulary skills answered direct questions more accurately if they were given the verbal labels interview than when they were not. Implications of the findings for memory performance of low-SES children are discussed. Copyright © 2014 John Wiley & Sons, Ltd.
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[Residues and health risk assessment of sulfonamides in sediment and fish from typical marine aquaculture regions of Guangdong Province, China].
Huan Jing Ke Xue
PUBLISHED: 09-24-2014
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Concentrations of sulfonamides including sulfadiazine (SDZ), sulfadimidin (SM2) and sulfamethoxazole (SMX) in sediments, muscle and liver tissues of 7 kinds of fish species collected from two marine aquaculture regions along the coast of Guangdong Provice were determined by high performance liquid chromatography (HPLC) equipped with a ultraviolet detector. Assessment of the health risks were conducted based on the values of maximum residue limits (MRL) and acceptable daily intake (ADI). The results showed that sulfonamides were found in all the sediment samples. The concentrations (dry wet) ranged from 2.1 - 35.2 ng x g(-1), the detected frequency of the 3 sulfonamide antibiotics ranked as SDZ (85.7%) > SM2 (71.4%) > SMX (28.6%). The detection rate of sulfonamides in samples from Daya Bay was higher than that from Hailing Island. Higher concentrations were detected in liver tissues rather than in muscle tissues (P < 0.05). The residues of SDZ, SM2 and SMX in fish muscle tissues (wet weight) ranged from 11.6-37.9, 16.3-27.8 and 4.9-20.0 ng x g(-1), respectively. The calculated daily intakes of sulfonamides in the present study ranged from 3.37-36.72 ng x kg(-1), which accounted for 0.007% -0.073% of the ADI (50 microg x kg(-1)). Health risks to human body were negligible as the estimated intake was less than 1% ADI, therefore the security of dietary was high.
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Workflow for combined proteomics and glycomics profiling from histological tissues.
Anal. Chem.
PUBLISHED: 09-24-2014
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Extracellular matrixes comprise glycoproteins, glycosaminoglycans and proteoglycans that order the environment through which cells receive signals and communicate. Proteomic and glycomic molecular signatures from tissue surfaces can add diagnostic power to the immunohistochemistry workflows. Acquired in a spatially resolved manner, such proteomic and glycomic information can help characterize disease processes and be easily applied in a clinical setting. Our aim toward obtaining integrated omics datasets was to develop the first workflow applicable for simultaneous analysis of glycosaminoglycans, N-glycans and proteins/peptides from tissue surface areas as small as 1.5 mm in diameter. Targeting small areas is especially important in the case of glycans, as their distribution can be very heterogeneous between different tissue regions. We first established reliable and reproducible digestion protocols for the individual compound classes by applying standards on the tissue using microwave irradiation to achieve reduced digestion times. Next, we developed a multienzyme workflow suitable for analysis of the different compound classes. Applicability of the workflow was demonstrated on serial mouse brain and liver sections, both fresh frozen and formalin-fixed. The glycomics data from the 1.5 mm diameter tissue surface area was consistent with data published on bulk mouse liver and brain tissues, which demonstrates the power of the workflow in obtaining combined molecular signatures from very small tissue regions.
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[Roles of adenosine receptors in Alzheimer's disease].
Yao Xue Xue Bao
PUBLISHED: 09-13-2014
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As an important neurotransmitter, adenosine displays its functions by acting on the adenosine receptors. Recent studies have shown that the distribution, expression and balance among subtypes of adenosine receptors are closely related with cognitive activities, and changes of adenosine receptors play key roles in neurodegenerative disorders including Alzheimer's disease. It has been pointed out that prolonged activation of adenosine receptors by high level adenosine may lead to the disturbance of balance among adenosine receptor subtypes. This imbalance mainly performed as increased expression of A2a receptor and decreased expression of A1 receptor, and enhancement of the excitatory signals mediated by A2a receptor and weakened inhibitory signals mediated by A1 receptor. Changes of these two subtypes of adenosine receptors may lead to a lot of disorders of neurological activities which developed into dysfunction of cognition to the end. These findings imply that the potential of maintaining the balance among adenosine receptors on the treatment of AD would facilitate both the revealing of the mechanism and the cure of AD.
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Interference with the Expression of ?-Catenin Reverses Cisplatin Resistance in A2780/DDP Cells and Inhibits the Progression of Ovarian Cancer in Mouse Model.
DNA Cell Biol.
PUBLISHED: 09-12-2014
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Cisplatin is a most active drug for the treatment of ovarian cancer; however, acquired cisplatin resistance is easily seen in patients with ovarian cancer. The aim of this study is to clarify the molecular mechanism of cisplatin resistance and try to reverse cisplatin resistance in ovarian cancer lines in vitro and in vivo. First, we used ovarian cancer cell line A2780, and its cisplatin-resistant subline, A2780/DDP as cell model. Cell viability was determined by MTT assay and the IC50 values were observed to increase in a dose- and time-dependent manner. Next, the expression of ?-catenin was determined by western blotting analysis, and the results demonstrated that the expression level of ?-catenin in A2780/DDP cells was significantly higher than that in A2780 cells (p<0.01). Moreover, we detected the distribution of cytoplasmic and nuclear ?-catenin by western blot analysis, which showed that ?-catenin was mainly located in nucleus. Compared with A2780 cells, there was no obvious change as the increasing dose of cisplatin in A2780/DDP cells reveal that cisplatin resistance was related to the exrpession of ?-catenin. Furthermore, interference with the expression of ?-catenin could effectively reverse cisplatin resistance as IC50 was significantly decreased from 123.7 to 42.43??M in A2780/DDP cells. Additionally, transient interference of ?-catenin by siRNA promoted the apoptosis of A2780/DDP cells, for increased apoptosis rates and cleaved caspase-3 levels were detected being treated with cisplatin. Finally, tumorigenicity experiments showed that tumor growth was significantly suppressed in ?-catenin shRNA group. The body weight was not significantly changed during the experimental days. In conclusion, all the results showed that cisplatin resistance was partly induced by Wnt/?-catenin signaling pathway. Interfering the expression of ?-catenin could reverse cisplatin resistance in vitro and in vivo. Thus, ?-catenin could be a potential therapeutic target for the therapy of cisplatin-resistant ovarian cancer.
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Emulsification of algal oil with soy lecithin improved DHA bioaccessibility but did not change overall in vitro digestibility.
Food Funct
PUBLISHED: 09-12-2014
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Oil emulsification facilitates digestive lipolysis and subsequent lipid bioaccessibility. This study aimed to understand the effects of emulsification on DHA-rich algal oil digestion and bioaccessibility. An oil/water emulsion (50?:?44?:?6 oil-water-soy lecithin) was subjected to an in vitro digestion model with gastric pH 1.6 or 4.0 and particle size distributions, duodenal stage lipolysis and DHA bioaccessibility were determined. The emulsion was destabilized at gastric pH 1.6, with subsequent slow duodenal lipolysis. With gastric pH 4.0, the emulsion structure remained intact, initial lipolysis proceeded rapidly and DHA bioaccessibility was higher than for bulk oil, a mixture of oil, water and soy lecithin, and the gastric pH 1.6 destabilized emulsion (p < 0.05). However, the extent of lipolysis was not affected by emulsification or gastric pH. Therefore, the presence of an intact emulsion at the start of duodenal digestion, while not impacting the extent of lipolysis, did impact the initial lipolysis and DHA bioaccessibility.
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Identification of Klebsiella pneumoniae strains harboring inactive extended-spectrum beta-lactamase antibiotic-resistance genes.
Chin. Med. J.
PUBLISHED: 09-06-2014
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The extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae has increasingly become a major contributor to nosocomial infections and can exhibit multiple antibiotic resistance. Previous studies have focused on the resistance genes in ESBL-producing strains, and the resistance-associated genetic environment of non-ESBL-producing strains has been ignored until now. Here, we investigated the occurrence and characteristics of non-ESBL-producing K. pneumoniae, which potentially carries unexpressed resistance genes.
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ALK-Dependent Control of Hypoxia-Inducible Factors Mediates Tumor Growth and Metastasis.
Cancer Res.
PUBLISHED: 09-05-2014
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Rearrangements involving the anaplastic lymphoma kinase (ALK) gene are defining events in several tumors, including anaplastic large-cell lymphoma (ALCL) and non-small cell lung carcinoma (NSCLC). In such cancers, the oncogenic activity of ALK stimulates signaling pathways that induce cell transformation and promote tumor growth. In search for common pathways activated by oncogenic ALK across different tumors types, we found that hypoxia pathways were significantly enriched in ALK-rearranged ALCL and NSCLC, as compared with other types of T-cell lymphoma or EGFR- and K-RAS-mutated NSCLC, respectively. Consistently, in both ALCL and NSCLC, we found that under hypoxic conditions, ALK directly regulated the abundance of hypoxia-inducible factors (HIF), which are key players of the hypoxia response in normal tissues and cancers. In ALCL, the upregulation of HIF1? and HIF2? in hypoxic conditions required ALK activity and its downstream signaling proteins STAT3 and C/EBP?. In vivo, ALK regulated VEGFA production and tumor angiogenesis in ALCL and NSCLC, and the treatment with the anti-VEGFA antibody bevacizumab strongly impaired ALCL growth in mouse xenografts. Finally, HIF2?, but not HIF1?, was required for ALCL growth in vivo whereas the growth and metastasis potential of ALK-rearranged NSCLC required both HIF1? and HIF2?. In conclusion, we uncovered an ALK-specific regulation of the hypoxia response across different ALK(+) tumor types and propose HIFs as a powerful specific therapeutic target in ALK-rearranged ALCL and NSCLC. Cancer Res; 74(21); 6094-106. ©2014 AACR.
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Role of the new rural cooperative medical system in alleviating catastrophic medical payments for hypertension, stroke and coronary heart disease in poor rural areas of China.
BMC Public Health
PUBLISHED: 09-02-2014
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Hypertension, stroke and coronary heart disease (CHD) are common diseases that impose a heavy burden on patients and their families, particularly on those living in poor areas. This study examined catastrophic medical payments faced by patients with these diseases and the effectiveness of the new rural cooperative medical system (NRCMS) at alleviating the impact of the said diseases in fourth-class rural areas (i.e. those with annual income of less than RMB 1500/$240.2 per capita) of China.
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Effects of acetaldehyde and L-carnitine on morphology and enzyme activity of myocardial mitochondria in rats.
Mol. Biol. Rep.
PUBLISHED: 09-02-2014
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This study aimed to investigate the effects of acetaldehyde (AA) and L-carnitine (LC) on morphology and enzyme activity of myocardial mitochondria in rats. Sixty-five Wistar rats were randomly divided into 4 groups: the control group (n = 20), the AA low-dose group (n = 15), the AA high-dose group (n = 15) and the AA + LC group (n = 15). Different doses (110 mg/kg and 220 mg/kg) AA was injected intraperitoneally once a day for 4 weeks. After 4 weeks administration, transmission electron microscope (TEM) observation of morphology of rat myocardial mitochondria was performed. Serum levels of succinate dehydrogenase (SDH), superoxide dismutase (SOD), malondialdehyde (MDA) and cardiac troponin I (cTnI) were detected to evaluate mitochondrial enzymes activities. Light micrograph of rat myocardiocytes in the control group showing normal architecture of myocytes. The numerical density and number of mitochondria in both low-dose and high-dose AA groups were lower than that of the control group. After administration of LC, the rats in the AA + LC group showed an obvious increase in the numerical density and number of mitochondria. TEM showed that both low-dose and high-dose AA could induce myocardial mitochondrial damage in rats in a dose-dependent manner, such as mitochondrial swelling, disruptions of crest and membrane, mitochondrial deficiency. The degree of mitochondrial damage of the AA + LC group was significantly decreased after administration of LC. Our results showed that serum levels of SDH and SOD in the AA + LC and control groups were also higher than those of the low-dose and high-dose AA groups; while the MDA level in the AA + LC and control groups were lower than that of the low-dose and high-dose AA groups. The low-dose AA, high-dose AA and AA + LC groups exhibited a higher level of serum cTnI than that of the control group. However, there was no significant difference in serum cTnI level among the low-dose AA, high-dose AA and AA + LC groups. Our findings indicate that AA may lead to myocardial mitochondrial damage and the induction of enzyme activity in rats, while administration of LC could alleviate AA-related damage of rat myocardial mitochondria.
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The structural basis of ATP as an allosteric modulator.
PLoS Comput. Biol.
PUBLISHED: 09-01-2014
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Adenosine-5'-triphosphate (ATP) is generally regarded as a substrate for energy currency and protein modification. Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP. Through extensive analysis of ATP in solution and proteins, we found that the free ATP can exist in the compact and extended conformations in solution, and the two different conformational characteristics may be responsible for ATP to exert distinct biological functions: ATP molecules adopt both compact and extended conformations in the allosteric binding sites but conserve extended conformations in the substrate binding sites. Nudged elastic band simulations unveiled the distinct dynamic processes of ATP binding to the corresponding allosteric and substrate binding sites of uridine monophosphate kinase, and suggested that in solution ATP preferentially binds to the substrate binding sites of proteins. When the ATP molecules occupy the allosteric binding sites, the allosteric trigger from ATP to fuel allosteric communication between allosteric and functional sites is stemmed mainly from the triphosphate part of ATP, with a small number from the adenine part of ATP. Taken together, our results provide overall understanding of ATP allosteric functions responsible for regulation in biological systems.
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Percutaneous retrieval of PICC fractures via the femoral vein in six cancer patients.
J Vasc Access
PUBLISHED: 09-01-2014
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To investigate the feasibility and safety of the interventional technique of retrieving the fractured peripherally inserted central catheter (PICC) segments within the vessels via the femoral vein.
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Effect of internal iliac artery chemotherapy after transurethral resection of bladder tumor for muscle invasive bladder cancer.
Chin. J. Cancer Res.
PUBLISHED: 08-31-2014
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To evaluate the clinical effect of transurethral resection of bladder tumor (TUR-BT) combined with internal iliac artery chemotherapy and intravesical instillation therapy for muscle invasive bladder cancer (MIBC).
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[Effects of polymorphisms in XRCC1 and APE1 on vinyl chloride-induced chromosome damage].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 08-30-2014
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To evaluate the effects of polymorphisms in XRCC1 and APE1 genes on vinyl chloride (VC)-induced chromosomal damage in peripheral lymphocytes.
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Core-Shell ?-Fe2 O3 @?-MoO3 Nanorods as Lithium-Ion Battery Anodes with Extremely High Capacity and Cyclability.
Chem Asian J
PUBLISHED: 08-28-2014
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?-Fe2 O3 nanoparticles are uniformly coated on the surface of ?-MoO3 nanorods through a two-step hydrothermal synthesis method. As the anode of a lithium-ion battery, ?-Fe2 O3 @?-MoO3 core-shell nanorods exhibit extremely high lithium-storage performance. At a rate of 0.1?C (10?h per half cycle), the reversible capacity of ?-Fe2 O3 @?-MoO3 core-shell nanorods is 1481?mA?h?g(-1) and a value of 1281?mA?h?g(-1) is retained after 50?cycles, which is much higher than that retained by bare ?-MoO3 and ?-Fe2 O3 and higher than traditional theoretical results. Such a good performance can be attributed to the synergistic effect between ?-Fe2 O3 and ?-MoO3 , the small size effect, one-dimensional nanostructures, short paths for lithium diffusion, and interface spaces. Our results reveal that core-shell nanocomposites have potential applications as high-performance lithium-ion batteries.
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Genomic and transcriptomic analysis of NDM-1 Klebsiella pneumoniae in spaceflight reveal mechanisms underlying environmental adaptability.
Sci Rep
PUBLISHED: 08-28-2014
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The emergence and rapid spread of New Delhi Metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae strains has caused a great concern worldwide. To better understand the mechanisms underlying environmental adaptation of those highly drug-resistant K. pneumoniae strains, we took advantage of the China's Shenzhou 10 spacecraft mission to conduct comparative genomic and transcriptomic analysis of a NDM-1 K. pneumoniae strain (ATCC BAA-2146) being cultivated under different conditions. The samples were recovered from semisolid medium placed on the ground (D strain), in simulated space condition (M strain), or in Shenzhou 10 spacecraft (T strain) for analysis. Our data revealed multiple variations underlying pathogen adaptation into different environments in terms of changes in morphology, H2O2 tolerance and biofilm formation ability, genomic stability and regulation of metabolic pathways. Additionally, we found a few non-coding RNAs to be differentially regulated. The results are helpful for better understanding the adaptive mechanisms of drug-resistant bacterial pathogens.
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Neuronal representation of working memory in the medial prefrontal cortex of rats.
Mol Brain
PUBLISHED: 08-28-2014
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Working memory is a process for short-term active maintenance of information. Behavioral neurophysiological studies in monkeys have demonstrated that the dorsolateral prefrontal cortex (dlPFC) is a key cortical region for working memory. The medial prefrontal cortex (mPFC) in rats is a cortical area similar to the dlPFC in monkeys in terms of anatomical connections, and is also required for behavioral performance on working-memory tasks. However, it is still controversial regarding whether and how mPFC neurons encode working memory. In the present study, we trained rats on a two-choice spatial delayed alternation task in Y maze, a typical working memory task for rodents, and investigated neuronal activities in the mPFC when rats performed the task. Our results show that, (1) inactivation of the mPFC severely impaired the performance of rats on the task, consistent with previous studies showing the importance of the mPFC for working-memory tasks; (2) 93.7% mPFC cells (449 in 479) exhibited changes in spiking frequency that were temporally locked with the task events, some of which, including delay-related cells, were tuned by spatial information; (3) differential delay activities in individual mPFC cells appeared transiently and sequentially along the delay, especially during the early phase of the delay; (4) some mPFC cells showed no change in discharge frequency but exhibited differential synchronization in firing during the delay. The present results suggest that mPFC neurons in rats are involved in encoding working memory, via increasing firing frequency or synchronization.
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Continual exposure to cigarette smoke extracts induces tumor-like transformation of human nontumor bronchial epithelial cells in a microfluidic chip.
J Thorac Oncol
PUBLISHED: 08-27-2014
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Heavy cigarette smoking-related chronic obstructive pulmonary disease is an independent risk factor for lung squamous carcinoma. However, the mechanisms underlying the malignant transformation of bronchial epithelial cells are unclear.
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Alcohol drinking and the risk of colorectal adenoma: a dose-response meta-analysis.
Eur. J. Cancer Prev.
PUBLISHED: 08-26-2014
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The International Agency for Research on Cancer concluded that alcohol consumption was positively related to colorectal cancer. However, the association between alcohol consumption and colorectal adenoma (CRA), the established precancerous lesion of colorectal cancer, remains unclear. We identified studies from a literature search of MEDLINE, EMBASE, and ISI Web of Science through 31 October 2013, and by searching reference lists of pertinent articles. Summary relative risks with 95% confidence intervals were calculated using a random-effects model. A total of 30 studies with 26?145 incident CRA cases were included. Overall, an increase of 25?g (two drinks) per day of alcohol consumption was related to an increased risk of CRA (summary relative risk=1.27, 95% confidence interval: 1.17-1.37). There was considerable heterogeneity between studies not explained by study design, sex, geographic location, publication year, site or size of the lesions, type of adenoma, number of cases, endoscopic assessment, or adjustment for main confounders. The positive association was evident for both men and women and for colonic adenoma, but not for rectal adenoma. Increased alcohol consumption is associated with an increased risk of CRA for both men and women and for adenoma in the colon, but not in the rectum.
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Therapeutic Effects of Fucoidan in 6-Hydroxydopamine-Lesioned Rat Model of Parkinson's disease: Role of NADPH oxidase-1.
CNS Neurosci Ther
PUBLISHED: 08-24-2014
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To explore the effect of fucoidan treatment on oxidative stress-mediated dopaminergic neuronal damage and its potential mechanisms.
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Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA Methylome analysis.
Cell Stem Cell
PUBLISHED: 08-21-2014
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In this study, we present integrated quantitative proteome, transcriptome, and methylome analyses of hematopoietic stem cells (HSCs) and four multipotent progenitor (MPP) populations. From the characterization of more than 6,000 proteins, 27,000 transcripts, and 15,000 differentially methylated regions (DMRs), we identified coordinated changes associated with early differentiation steps. DMRs show continuous gain or loss of methylation during differentiation, and the overall change in DNA methylation correlates inversely with gene expression at key loci. Our data reveal the differential expression landscape of 493 transcription factors and 682 lncRNAs and highlight specific expression clusters operating in HSCs. We also found an unexpectedly dynamic pattern of transcript isoform regulation, suggesting a critical regulatory role during HSC differentiation, and a cell cycle/DNA repair signature associated with multipotency in MPP2 cells. This study provides a comprehensive genome-wide resource for the functional exploration of molecular, cellular, and epigenetic regulation at the top of the hematopoietic hierarchy.
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Size-based cell sorting with a resistive pulse sensor and an electromagnetic pump in a microfluidic chip.
Electrophoresis
PUBLISHED: 08-21-2014
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An electrokinetic microfluidic chip is developed to detect and sort target cells by size from human blood samples. Target-cell detection is achieved by a differential resistive pulse sensor (RPS) based on the size difference between the target cell and other cells. Once a target cell is detected, the detected RPS signal will automatically actuate an electromagnetic pump built in a microchannel to push the target cell into a collecting channel. This method was applied to automatically detect and sort A549 cells and T-lymphocytes from a peripheral fingertip blood sample. The viability of A549 cells sorted in the collecting well was verified by Hoechst33342 and propidium iodide staining. The results show that as many as 100 target cells per minute can be sorted out from the sample solution and thus is particularly suitable for sorting very rare target cells, such as circulating tumor cells. The actuation of the electromagnetic valve has no influence on RPS cell detection and the consequent cell-sorting process. The viability of the collected A549 cell is not impacted by the applied electric field when the cell passes the RPS detection area. The device described in this article is simple, automatic, and label-free and has wide applications in size-based rare target cell sorting for medical diagnostics.
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A tetrameric cage with D2h symmetry through alkyne metathesis.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-21-2014
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Shape-persistent covalent organic polyhedrons (COPs) with ethynylene linkers are usually prepared through kinetically controlled cross-coupling reactions. The high-yielding synthesis of ethynylene-linked rigid tetrameric cages via one-step alkyne metathesis from readily accessible triyne precursors is presented. The tetrameric cage contains two macrocyclic panels and exhibits D2h symmetry. The assembly of such a COP is a thermodynamically controlled process, which involves the initial formation of macrocycles as key intermediates followed by the connection of two macrocycles with ethynylene linkages. With a large internal cavity, the cage exhibits a high binding selectivity toward C70 (K = 3.9×10(3) L?mol(-1)) over C60 (no noticeable binding).
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ABCB1 C3435T polymorphism and the risk of ischemic heart disease: a meta-analysis.
Genet Test Mol Biomarkers
PUBLISHED: 08-13-2014
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ATP binding cassette transporter 1 (ABCB1) plays a critical role in the development and progression of cardiovascular disease. Emerging evidence suggests that common functional polymorphisms in the ABCB1 gene might have an impact on an individual's susceptibility to ischemic heart disease, but individually published results are inconclusive. The MEDLINE (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013), and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Meta-analysis was performed with the use of the STATA statistical software. Odds ratios (OR) with their 95% confidence intervals (95% CIs) were calculated. Seven case-control studies with a total of 2310 myocardial infarction (MI) patients and 10,506 acute coronary syndrome (ACS) patients met the inclusion criteria. Our meta-analysis results indicated that ABCB1 C3435T polymorphism may be associated with an increased risk of MI and ACS, especially among Asian populations (T allele vs. C allele: OR=1.40, 95% CI=1.31-1.49, ph=0.058). Meta-regression analyses showed that clinical subtype and ethnicity may be the main sources of heterogeneity (T allele vs. C allele: OR=1.16, 95% CI=0.97-1.37, ph=0.036). Our findings provide empirical evidence that ABCB1 C3435T polymorphism may contribute to the risk of MI and ACS, especially among Caucasian populations. Thus, detection of ABCB1 C3435T polymorphism may be a promising biomarker for the early detection of MI and ACS.
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Modulation of platelet activation and thrombus formation using a pan-PI3K inhibitor S14161.
PLoS ONE
PUBLISHED: 08-12-2014
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The phosphatidylinositol 3-kinase (PI3K) signaling pathway is critical in modulating platelet functions. In the present study, we evaluated the effect of S14161, a recently identified pan-class I PI3K inhibitor, on platelet activation and thrombus formation. Results showed that S14161 inhibited human platelet aggregation induced by collagen, thrombin, U46619, and ADP in a dose-dependent manner. Flow cytometric studies showed that S14161 inhibited convulxin- or thrombin-induced P-selectin expression and fibrinogen binding of single platelet. S14161 also inhibited platelet spreading on fibrinogen and clot retraction, processes mediated by outside-in signaling. Using a microfluidic chamber we demonstrated that S14161 decreased platelet adhesion on collagen-coated surface by about 80%. Western blot showed that S14161 inhibited phosphorylation of Akt at both Ser473 and Thr308 sites, and GSK3? at Ser9 in response to collagen, thrombin, or U46619. Comparable studies showed that S14161 has a higher potential bioavailability than LY294002, a prototypical inhibitor of pan-class I PI3K. Finally, the effects of S14161 on thrombus formation in vivo were measured using a ferric chloride-induced carotid artery injury model in mice. The intraperitoneal injection of S14161 (2 mg/kg) to male C57BL/6 mice significantly extended the first occlusion time (5.05 ± 0.99 min, n = 9) compared to the vehicle controls (3.72 ± 0.95 min, n = 8) (P<0.05), but did not prolong the bleeding time (P>0.05). Taken together, our data showed that S14161 inhibits platelet activation and thrombus formation without significant bleeding tendency and toxicity, and considering its potential higher bioavailability, it may be developed as a novel therapeutic agent for the prevention of thrombotic disorders.
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Graphene/graphite sheet assisted growth of high-areal-density horizontally aligned carbon nanotubes.
Chem. Commun. (Camb.)
PUBLISHED: 08-12-2014
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We report a facile graphene/graphite sheet assisted CVD process for the synthesis of high-areal-density HACNT arrays. Besides, some metal nanoparticles could eat the graphene/graphite sheets, forming serpentine holes on the sheets in the early stage, and finally leading to the precipitation of CNTs without an additional carbon source.
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p53 is required for cisplatin-induced processing of the mitochondrial fusion protein L-Opa1 that is mediated by the mitochondrial metallopeptidase Oma1 in gynecologic cancers.
J. Biol. Chem.
PUBLISHED: 08-11-2014
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Mitochondria are highly dynamic organelles, and mitochondrial fission is a crucial step of apoptosis. Although Oma1 is believed to be responsible for long form Opa1 (L-Opa1) processing during mitochondrial fragmentation, whether and how Oma1 is involved in L-Opa1 processing and participates in the regulation of chemoresistance is unknown. Chemosensitive and chemoresistant ovarian (OVCA) and cervical (CECA) cancer cells were treated with cisplatin (CDDP). Mitochondrial dynamics and protein contents were assessed by immunofluorescence and Western blot, respectively. The requirements of Oma1 and p53 for CDDP-induced L-Opa1 processing, mitochondrial fragmentation, and apoptosis were examined by siRNA or cDNA. CDDP induces L-Opa1 processing and mitochondrial fragmentation in chemosensitive but not in chemoresistant cells. CDDP induced Oma1 40-kDa form increases in OV2008 cells, not in C13* cells. Oma1 knockdown inhibited L-Opa1 processing, mitochondrial fragmentation, and apoptosis. Silencing p53 expression attenuated the effects of CDDP in Oma1 (40 kDa) increase, L-Opa1 processing, mitochondrial fragmentation, and apoptosis in chemosensitive OVCA cells, whereas reconstitution of p53 in p53 mutant or null chemoresistant OVCA cells induced Oma1 (40 kDa) increase, L-Opa1 processing, mitochondrial fragmentation, and apoptosis irrespective of the presence of CDDP. Prohibitin 1 (Phb1) dissociates from Opa1-Phb1 complex and binds phosphorylated p53 (serine 15) in response to CDDP in chemosensitive but not chemoresistant CECA cells. These findings demonstrate that (a) p53 and Oma1 mediate L-Opa1 processing, (b) mitochondrial fragmentation is involved in CDDP-induced apoptosis in OVCA and CECA cells, and (c) dysregulated mitochondrial dynamics may in part be involved in the pathophysiology of CDDP resistance.
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Postmortem urinary catecholamine levels with regard to the cause of death.
Leg Med (Tokyo)
PUBLISHED: 08-08-2014
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Previous studies suggested that serum catecholamines are useful for investigating stress responses in the death process. The present study analyzed postmortem urinary adrenaline (Ad), noradrenaline (Nad) and dopamine (DA) in serial forensic autopsy cases (n=199: 154 males and 45 females; age >9years; survival time <0.5-168h; within 10days postmortem) to investigate the differences among the causes of death with special regard to hyperthermia (heatstroke; n=11) and hypothermia (cold exposure; n=10); other cases included fatalities from injury (n=47), mechanical asphyxiation (n=18), drowning (n=14), intoxication (n=31), fire fatality (n=33) and natural death (n=35). Each catecholamine level in urine was independent of the age or gender of the subjects, postmortem interval over 10days or survival time, and did not correlate with the blood level. Urinary Adr and Nad levels were similar to those of clinical serum reference ranges, while DA was higher in all cases. Adr and Nad were higher in blunt head injury, methamphetamine abuse, hypothermia (cold exposure) and hyperthermia (heat stroke), but were low in mechanical asphyxia, drowning, fire fatality, sedative-hypnotic intoxication and acute cardiac death. DA was higher in injury, drowning, fire fatality, methamphetamine abuse and acute cardiac death, but was lower in mechanical asphyxiation and sedative-hypnotic intoxication. These profiles were quite different from those of serum levels, involving a predominant increase of DA, and may be useful for differentiating hyperthermia (heatstroke) and hypothermia (cold exposure) from drowning, sedative-hypnotic intoxication and sudden cardiac death.
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The impact of changes in source water quality on trihalomethane and haloacetonitrile formation in chlorinated drinking water.
Chemosphere
PUBLISHED: 08-04-2014
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This study examined the formation of disinfection by-products (DBPs), including nitrogenous DBPs, haloacetonitriles (HANs), and carbonaceous DBPs, trihalomethanes (THMs), upon chlorination of water samples collected from a conventional Chinese surface water treatment plant (i.e. applying coagulation, sedimentation, and filtration). Reductions in the average concentrations (and range, shown in brackets) of dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) from 4.8 (3.0-7.3) ?g/L and 0.52 (0.20-0.81) ?g/L in 2010 to 2.4 (1.4-3.7) ?g/L and 0.17 (0.11-0.31) ?g/L in 2012, respectively, led to a decrease in HANs and THMs from 5.3 and 28.5?g/L initially to 0.85 and 8.2?g/L, as average concentrations, respectively. The bromide concentration in the source water also decreased from 2010 to 2012, but the bromine incorporation factor (BIF) for the THMs did not change significantly; however, for HAN the BIFs increased because the reduction in DON was higher than that of bromide. There was good linear relationship between DOC and THM concentrations, but not between DON and HANs.
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Spectroscopic analyses and studies on respective interaction of cyanuric acid and uric acid with bovine serum albumin and melamine.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 07-30-2014
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In this work, the fluorescence quenching was used to study the interaction of cyanuric acid (CYA) and uric acid (UA) with bovine serum albumin (BSA) at two different temperatures (283 K and 310 K). The bimolecular quenching constant (Kq), apparent quenching constant (Ksv), effective binding constant (KA) and corresponding dissociation constant (KD), binding site number (n) and binding distance (r) were calculated by adopting Stern-Volmer, Lineweaver-Burk, Double logarithm and overlap integral equations. The results show that CYA and UA are both able to obviously bind to BSA, but the binding strength order is BSA+CYA
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Loss of PEG chain in routine SDS-PAGE analysis of PEG-maleimide modified protein.
Electrophoresis
PUBLISHED: 07-29-2014
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SDS-PAGE represents a quick and simple method for qualitative and quantitative analysis of protein and protein-containing conjugates, mostly pegylated proteins. PEG-maleimide (MAL) is frequently used to site-specifically pegylate therapeutic proteins via free cysteine residue by forming a thiosuccinimide structure for pursuing homogeneous products. The C-S linkage between protein and PEG-MAL is generally thought to be relatively stable. However, loss of intact PEG chain in routine SDS-PAGE analysis of PEG-maleimide modified protein was observed. It is a thiol-independent thioether cleavage and the shedding of PEG chain exclusively happens to PEG-MAL modified conjugates although PEG-vinylsulfone conjugates to thiol-containing proteins also through a C-S linkage. Cleavage kinetics of PEG40k-MAL modified ciliary neurotrophic factor showed this kind of degradation could immediately happen even in 1 min incubation at high temperature and could be detected at physiological temperature and pH, although the rate was relatively slow. This may provide another degradation route for maleimide-thiol conjugate irrespective of reactive thiol, although the specific mechanism is still not very clear for us. It would also offer a basis for accurate characterization of PEG-MAL modified protein/peptide by SDS-PAGE analysis.
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The inhibition of fluorescence resonance energy transfer between multicolor quantum dots for rapid and sensitive detection of Staphylococcus aureus.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 07-24-2014
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In this paper, we constructed the fluorescence resonance energy transfer (FRET) system between two multi-color quantum dots (QDs) of two sizes for rapid and sensitive detection of Staphylococcus aureus. In this system, green-emitting QDs conjugated with rabbit anti-S. aureus antibodies were used as energy donors while orange-emitting QDs conjugated with goat-anti-rabbit IgG were used as energy acceptors to form FRET system. Pre-binding of Staphylococcus aureus (S. aureus) on the donor occupied the binding sites and thus blocked resonance energy transfer between two colors QDs, leading to the quenching fluorescence of the acceptor. The fluorescence of acceptor has a linear calibration graph with the concentrations of S. aureus from 52 to 2.6×10(5) CFU mL(-1). The low detection limit was 10 CFU/mL. It was worth mentioning that the detection method of S. aureus had been applied to the analysis of apple juice and milk samples, which could potentially be developed into a sensor in the further study.
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Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation.
Cell
PUBLISHED: 07-15-2014
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While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of transcript function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%-99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9. Together they enable modulation of gene expression over a ?1,000-fold range. Using these rules, we construct genome-scale CRISPRi and CRISPRa libraries, each of which we validate with two pooled screens. Growth-based screens identify essential genes, tumor suppressors, and regulators of differentiation. Screens for sensitivity to a cholera-diphtheria toxin provide broad insights into the mechanisms of pathogen entry, retrotranslocation and toxicity. Our results establish CRISPRi and CRISPRa as powerful tools that provide rich and complementary information for mapping complex pathways.
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A peptide probe for the detection of neurokinin-1 receptor by disaggregation enhanced fluorescence and magnetic resonance signals.
Sci Rep
PUBLISHED: 07-09-2014
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We report a novel peptide probe for the detection of neurokinin-1 receptor using disaggregation-caused signal enhancement. The probe was obtained via the aggregation of a modified substance P in a terpyridine-Fe (II) complex with Gd (III)-DOTA into well-defined nanostructures, which effectively weaken ligand fluorescence and slow the exchange rate of inner-sphere water molecules. This probe disaggregates upon binding to the neurokinin-1 receptor and activates the contrast agents to generate a fluorescent signal that positively enhances magnetic resonance imaging contrast and allows for the detection of overexpressed receptors on tumor cells and the identification of lung cancer using serum samples.
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A drug-perfluorocarbon nanoemulsion with an ultrathin silica coating for the synergistic effect of chemotherapy and ablation by high-intensity focused ultrasound.
Adv. Mater. Weinheim
PUBLISHED: 07-04-2014
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The synergistic effect of chemotherapy and ablation using high-intensity focused ultrasound (HIFU) is realized with a newly developed drug-delivery system. The system comprises an ultrathin silica shell surrounding a poly(lactic-co-glycolic acid) nanoemulsion core containing the drug (CPT) and a perfluorocarbon (PFOB). This nanosystem presents many advantages in drug delivery, such as excellent structural stability, high drug-loading capacity, and rapid HIFU-mediated drug release.
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Structure of human SNX10 reveals insights into its role in human autosomal recessive osteopetrosis.
Proteins
PUBLISHED: 07-03-2014
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Sorting nexin 10 (SNX10), the unique member of the SNX family having vacuolation activity in cells, was shown to be involved in the development of autosomal recessive osteopetrosis (ARO) in recent genetic studies. However, the molecular mechanism of the disease-related mutations affecting the biological function of SNX10 is unclear. Here, we report the crystal structure of human SNX10 to 2.6Å resolution. The structure reveals that SNX10 contains the extended phox-homology domain we previously proposed. Our study provides the structural details of those disease-related mutations. Combined with the vacuolation study of those mutations, we found that Tyr32 and Arg51 are important for the protein stability and both play a critical role in vacuolation activity, while Arg16Leu may affect the function of SNX10 in osteoclast through protein-protein interactions. Proteins 2014; 82:3483-3489. © 2014 Wiley Periodicals, Inc.
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A Non-Doped Phosphorescent Organic Light-Emitting Device with Above 31% External Quantum Efficiency.
Adv. Mater. Weinheim
PUBLISHED: 07-02-2014
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The demonstrated square-planar Pt(II)-complex has reduced triplet-triplet quenching and therefore a near unity quantum yield in the neat thin film. A non-doped phosphorescent organic light-emitting diode (PhOLED) based on this emitter achieves (31.1 ± 0.1)% external quantum efficiency without any out-coupling, which shows that a non-doped PhOLED can be comparable in efficiency to the best doped devices with very complicated device structure.
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Clinical features of severe cases of hand, foot and mouth disease with EV71 virus infection in China.
Arch Med Sci
PUBLISHED: 06-27-2014
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Hand, foot and mouth disease (HFMD) caused by EV71 infection has become one of the major public health issues in China, which deeply affects children's health. The prevention and control of EV71 is a challenge currently because there is no safe and effective vaccine or antiviral medications available.
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Effects of sevoflurane on leucine-rich repeat kinase 2-associated Drosophila model of Parkinson's disease.
Mol Med Rep
PUBLISHED: 06-24-2014
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Patients with Parkinson's disease (PD) often require surgery, and therefore may receive inhalation anesthesia. However, it is currently unknown whether inhalation anesthetics affect the prognosis of the disease. Leucine?rich repeat kinase 2 (LRRK2) genetic mutations are the most common cause of familial PD, contributing to ~39% of all cases in certain populations. The aim of the present study was to determine the effects of inhaled anesthetics on PD, by observing the influence of sevoflurane on a LRRK2?associated Drosophila model of PD. PD transgenic Drosophila overexpressing LRRK2 were generated by crossing flies expressing an LRRK2 upstream activation sequence, with tyrosine hydroxylase (TH)?Gal4 flies. Western blot analysis successfully verified that the transgenic Drosophila overexpressed LRRK2. Three days prior to eclosion, three genotypes of Drosophila were divided into four groups, and were exposed to air, 1, 2, or 3% sevoflurane, for 5 hours. Twenty?four hours after the exposure, the electrophysiological activities of the projection neurons (PN) in the brains of the Drosophila were recorded using a patch clamp. The locomotor activities were tested on days 5, 10, 15, 20, 25, 30, 35 and 40 following eclosion. The frequency of miniature excitatory synaptic currents (mEPSCs) obtained from the PNs of the TH?wild type LRRK2 (TH?WT) Drosophila brain, following exposure to air (1.60±0.05 Hz), was lower as compared with the wild type LRRK2 (WT) (2.51±0.07 Hz) and W1118 (2.41±0.10 Hz) Drosophila. After exposure to 1, 2 and 3% sevoflurane, the frequency of mEPSCs in the brains of the TH?WT group decreased to 0.82±0.04 Hz, 0.63±0.16 Hz and 0.55±0.04 Hz, respectively. The percentage decrease of the frequency of mEPSCs, from exposure to air to 1% sevoflurane, of the TH?WT group (48.32%±3.08%) was significantly higher, as compared with the WT (39.17%±1.42%) and W1118 (35.10%±2.66%) groups, and there was no statistical difference between the WT and W1118 groups. The transgenic TH?WT Drosophila presented an early decrease in locomotor ability, as compared with the WT and W1118 groups. Following a 5 hour exposure to sevoflurane, the percentage decrease of the climbing abilities of the TH?WT group, from exposure to air to 1% sevoflurane, were significantly lower, as compared with the WT and W1118 groups. In conclusion, sevoflurane had negative effects on the control W1118 flies, and also severely aggravated the prognosis of PD in the LRRK2?associated Drosophila model, through synaptic cholinergic deficits and impairment on locomotor abilities.
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The primary evaluation and characterization of obsolete DDT pesticide from a precalciner of a cement kiln.
Environ Technol
PUBLISHED: 06-23-2014
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1,1,1-Trichloro-2,2-bi(4-chlorophenyl)ethane (DDT) pesticide that has been extensively used in agriculture in China in the last century, and even now, has been banned from all purposes. The disposal of obsolete DDT pesticide has been an urgent task for the Chinese government. In order to evaluate the feasibility of co-processing DDT in the current new style dry-process rotary kiln with a precalciner as the feeding point, the destruction efficiency (DE) of DDTs (including p,p(')-DDT, o,p(')-DDT, p,p(')-DDE and p,p(')-DDD), proportion of DDTs in the combustion residue and exhaust gas, and the release of chlorine were studied under different operating conditions of temperature, oxygen content and gas retention time in the laboratory. The DE of DDTs exceeded 99% when the temperature was over 800 °C with enough oxygen. As the temperature increased from 600 °C to 1200 °C, the proportion of p,p(')-DDD increased and p,p(')-DDT decreased but still the main effective component remained in the combustion residue. In the exhaust gas, the most dominant phenomenon was the rapid increase in p,p(')-DDE concentration as the temperature increased. The release of chlorine reached a peak between 800 °C and 900 °C. It was found that the oxygen content had a positive correlation with the process of dechlorination. The proportion of p,p(')-DDE increased as the oxygen content was increased in the exhaust gas. The gas retention time had almost no influenced on the DE of DDTs, but affected the degradation extent of DDTs in the gas phase. These experiments showed that co-processing of obsolete DDT pesticide in cement kiln precalciners is feasible.
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Efficacy of single-layer continuous suture of the posterior wall in anastomosis involving a difficult location of the digestive tract.
Oncol Lett
PUBLISHED: 06-19-2014
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Surgery for digestive tract disease predominantly consists of reconstruction and anastomosis. Due to the difficult location, anastomosis is extremely challenging and the risk of complication increases accordingly. Traditional manual anastomosis and the application of a stapling device are insufficient. Therefore, the aim of this study was to investigate the feasibility and safety of a novel manual method in a difficult anastomotic location, consisting of a single-layer continuous suture in the posterior wall. In total, 15 beagle dogs were included in the study; eight underwent surgery with the novel manual method for reconstruction and anastomosis of the digestive tract, while seven underwent surgery with the stapler device as a control. The subsequent postoperative complications were observed and, three months later, the anastomotic ports were excised, and the pathological formation and morphological changes were evaluated. No statistically significant differences were identified between the total (50.0 vs. 57.1%; P=0.782) and anastomotic (0.0 vs. 28.6%; P=0.200) complication rates in the manual suture and staple suture groups, respectively. Compared with the control group, the operative expenditure was lower in the manual group (1726.7±33.5 vs. 2135.7±43.1 renminbi; P=0.001), the diameter of the anastomotic port was larger in the manual group (3.04±0.07 vs. 2.24±0.25 cm; P=0.004) and the thickness of the anastomotic port (in cm) was thinner in the manual group (2.94±0.06 vs. 5.07±0.85; P=0.002). Furthermore, the pathological formation of the anastomositic port in the manual group was improved. The results of the current study suggest single-layer continuous suture of the posterior wall in anastomosis of the digestive tract to be a novel method with feasibility and safety, particularly in difficult anastomotic locations.
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Association of rs9340799 polymorphism in estrogen receptor alpha gene with the risk of osteoarthritis: evidence based on 8,792 subjects.
Mol. Genet. Genomics
PUBLISHED: 06-11-2014
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Osteoarthritis (OA) is one of the most common skeletal disease, which seriously affects the quality of life of patients, particularly in the middle-aged and elderly individuals. We aimed to explore whether rs9340799 [estrogen receptor alpha (ER-?) XbaI A/G] polymorphism was associated with OA using a meta-analysis. A literature search for eligible studies published before March 28, 2014 was conducted in the PubMed, Web of Science, Embase, Cochrane database, Current Controlled Trials, Clinicaltrials.gov, Chinese Clinical Trial Registry, CBMdisc, CNKI, Google Scholar and Baidu Library. The association between the rs9340799 polymorphism and OA risk was assessed by odds ratios (ORs) together with their 95 % confidence intervals (CIs). A total of 663 articles were found. After article review and quality assessment, 10 articles involving 2,924 OA cases and 5,868 controls were included in the final meta-analysis. The combined evidence suggested that rs9340799 polymorphism contributed significantly to an increased risk of OA (for G allele vs. A allele: OR = 1.21, 95 % CI 1.03-1.43, p = 0.02; for G/G vs. A/A: OR = 1.30, 95 % CI 1.07-1.57, p = 0.009). In the subgroup analyses, significant associations were found between the rs9340799 polymorphism and the OA risk in the European group, Asian group, and knee osteoarthritis group, respectively. These results suggested that the rs9340799 polymorphism might be associated with the risk of OA. However, the results should be interpreted with caution because of the publication bias.
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Perspective on polychlorinated dibenzo-p-dioxin and dibenzofuran emissions during chemical production in China: an overlooked source of contemporary relevance.
Environ Sci Pollut Res Int
PUBLISHED: 06-07-2014
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Polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDDs/DFs) are pollutants of significant global concern, and China with its large size and industries is one of the main dioxin-emitting countries in the world. PCDDs/DFs may be formed during the manufacture of chemicals and can either remain in the products as impurities or be emitted into the environment or residues disposed to landfills. The uncertainties in the environmental emissions of PCDDs/DFs from the chemical production industry in China are large because of the complex nature of the industry and variability in the technologies used and limited monitoring conducted. In the current study, we used the PCDD/DF emission factor from the updated United Nations Environment Programme (UNEP) toolkit 2013, information from otherwise published data, and the chemical production data in 2010 to estimate PCDD/DF emissions from the chemical productions in China. Based on these data, it was estimated that there is 1480 g toxic equivalent (TEQ) from the chemical production industry in China, which is much higher than the value that was estimated and used in the national implementation plans (NIPs) for China (102.4 g TEQ in 2004). These results indicate that current PCDD/DF emissions from the chemical production industry in China may be overlooked. Therefore, we suggest that attention should be paid to PCDD/DF emissions from the chemical production industry in future updates of the Chinese NIP and that appropriate measures to decrease PCDD/DF emissions should be taken by better monitoring of products and processes in chemical production industry.
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A Sensitive and Selective Fluorimetric Method of Quick Determination of Sialic Acids in Egg Products by Lectin-CdTe Quantum Dots as Nanoprobe.
J. Food Sci.
PUBLISHED: 06-05-2014
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Sialic acids (SA) are widely found as components of oligosaccharide units in mucins, glycoproteins and other microbial polymers in nature food. The aim of this study is to create a new fluorimetric detection method applied for determinating SA in egg products by using a sensitive lectin-CdTe quantum dots (QDs) nanoprobe. Water-soluble and high luminescent CdTe QDs were conjugated with sambucus nigra bark lectin (SNA) as probe for SA detection. As a result of specific interaction between SA and SNA-CdTe QDs, the conjugations finally lead to the change of a fluorescent signal. Under optimal conditions, fluorescence intensity increase linearly with the increase of the concentration of SA ranging from 12 to 680 ng/mL. The low detection limit is 0.67 ng/mL. This quick and selective analysis method for SA detection has been used in synthetic samples and egg products with recovery between 97.92% and 110.42%, which demonstrates the application of this assay is feasible and practical.
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A Protein-Tagging System for Signal Amplification in Gene Expression and Fluorescence Imaging.
Cell
PUBLISHED: 06-01-2014
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Signals in many biological processes can be amplified by recruiting multiple copies of regulatory proteins to a site of action. Harnessing this principle, we have developed a protein scaffold, a repeating peptide array termed SunTag, which can recruit multiple copies of an antibody-fusion protein. We show that the SunTag can recruit up to 24 copies of GFP, thereby enabling long-term imaging of single protein molecules in living cells. We also use the SunTag to create a potent synthetic transcription factor by recruiting multiple copies of a transcriptional activation domain to a nuclease-deficient CRISPR/Cas9 protein and demonstrate strong activation of endogenous gene expression and re-engineered cell behavior with this system. Thus, the SunTag provides a versatile platform for multimerizing proteins on a target protein scaffold and is likely to have many applications in imaging and controlling biological outputs.
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Phenolic metabolite profiles and antioxidants assay of three Iridaceae medicinal plants for traditional Chinese medicine "She-gan" by on-line HPLC-DAD coupled with chemiluminescence (CL) and ESI-Q-TOF-MS/MS.
J Pharm Biomed Anal
PUBLISHED: 05-16-2014
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An on-line analysis method by HPLC-DAD coupled with chemiluminescence (CL) and ESI-Q-TOF-MS/MS was established for simultaneous detection and identification of antioxidants in three original plants of traditional Chinese medicine "She-gan". Two new isoflavonoid glycosides, along with 48 known compounds, including isoflavonoid glycosides and their aglycones, xanthones, flavones and other phenolic compounds, were identified or tentatively identified from the rhizomes of three Iridaceae plants, namely, Belamcanda chinensis, Iris tectorum and Iris dichotoma, which were used as "She-gan" in China. Among those compounds, isoflavone glycosides of iristectorigenin A and its isomers exhibited obviously inhibit CL, which suggested their strong free radical scavenging activity. The chemometric methods dealing with the data gained by chromatographic and antioxidant activity profiles exhibited the "similarities" and "differences" of chemical constituents and antioxidant activities for three studied Iridaceae species. The results indicated that the established method might provide for qualitative and quantitative evaluation of the herbal medicines.
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Investigating the Photostability of Quantum Dots at the Single-Molecule Level.
Chem Asian J
PUBLISHED: 04-29-2014
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Quantum dots (QDs) have shown great potential to provide spatial, temporal, and structural information for biological systems. However, blinking, photobleaching, and spectral blueshift are adverse effects on their practical applications in biomedical research. An investigation of the effects of six reducing agents including cysteine (Cys), 1,4-dithiothreitol (DTT), ethyl gallate (EG), L-glutathione (GSH), mercaptoacetic acid (MAA), and thiourea (TU) on the photostability of single QDs was studied. Our experiments demonstrate that both DTT and EG effectively inhibit blinking, photobleaching, and spectral blueshift. GSH molecules block blinking and photobleaching of QDs. The other reagents, Cys, MAA, and TU, only have the ability to counteract blinking. Possible explanations are given on the basis of research evidence. The results suggest possibilities for significant improvements in QDs for biological applications by adjusting the environmental conditions.
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Synergetic effects of hBMSCs and hPCs in osteogenic differentiation and their capacity in the repair of critical-sized femoral condyle defects.
Mol Med Rep
PUBLISHED: 04-28-2014
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Tissue-engineered bone grafts require an osteoblastic cellular source to be utilized in bone transplantation therapy. Human bone marrow stem cells (hBMSCs) and periosteal-derived stem cells (hPCs) are the commonly used cellular sources for bone tissue engineering and are essential in fracture healing. In the present study, hBMSCs and hPCs were co-cultured from the same donors, as the cellular source. In monolayer cultivation, co-culturing hBMSCs and hPCs demonstrated more robust mineralized nodule formation and stronger alkaline phosphatase (ALP) positive staining than hBMSCs or hPCs. Three-dimensional (3-D) culturing on porous ?-tricalcium phosphate (TCP) scaffolds and co-culturing of hBMSCs and hPCs significantly promoted the osteogenic specific mRNA expression of COL1?1, BMP-2, osteopontin (OPN) and osteocalcin (OC). For in vivo bone formation and neovascularization assessment, the cellular-?-TCP scaffolds were transplanted into critical-sized femoral condyle defects in rabbits. The results confirmed that co-culturing hBMSCs and hPCs accelerated bone regeneration and enhanced mature bone formation, but also facilitated central vascularization in scaffold pores. Based on these data, we recommend co-culturing hBMSCs and hPCs as a promising cellular source for bone tissue engineering applications.
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A versatile framework for microbial engineering using synthetic non-coding RNAs.
Nat. Rev. Microbiol.
PUBLISHED: 04-17-2014
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Synthetic non-coding RNAs have emerged as a versatile class of molecular devices that have a diverse range of programmable functions, including signal sensing, gene regulation and the modulation of molecular interactions. Owing to their small size and the central role of Watson-Crick base pairing in determining their structure, function and interactions, several distinct types of synthetic non-coding RNA regulators that are functional at the DNA, mRNA and protein levels have been experimentally characterized and computationally modelled. These engineered devices can be incorporated into genetic circuits, enabling the more efficient creation of complex synthetic biological systems. In this Review, we summarize recent progress in engineering synthetic non-coding RNA devices and their application to genetic and cellular engineering in a broad range of microorganisms.
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Reproductive health service use and social determinants among the floating population: a quantitative comparative study in Guangzhou City.
BMC Health Serv Res
PUBLISHED: 03-12-2014
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BackgroundThe World Health Assembly has pledged to achieve universal reproductive health (RH) coverage by 2015. Therefore, China has been vigorously promoting the equalisation of basic public health services (i.e. RH services). The floating population (FP) is the largest special group of internal migrants in China and constitutes the current national focus. However, gaps exist in the access of this group to RH services in China.MethodsA total of 453 members of the FP and 794 members of the residential population (RP) aged 18 to 50 years from five urban districts in Guangzhou City were recruited to participate in a cross-sectional survey in 2009. Information on demographics and socioeconomic status (SES) were collected from these two groups to evaluate the utilisation of RH knowledge and skills and family planning services (FPS), and to identify social determinants.ResultsThe proportion of individuals with low SES in the FP (19.2%) was higher than that in the RP (6.3%) (P <0.001). Of the FP, 9.7% to 35.8% had no knowledge of at least one skill, a proportion higher than the counterpart values (6.2% to 27.5%) for the RP (P <0.05). The frequency of FPS use among the FP and RP was low. However, FPS use was higher among the FP than among the RP (3.51 vs. 2.99) (P =0.050). Logistic regression analysis was used to analyse the social determinants that influence FPS use in the FP and RP. The factors that affect FPS utilisation of the RP included SES (OR =4.652, 95% CI =1.751, 12.362), whereas those of the FP excluded SES.ConclusionsThe FPS use of the FP in Guangzhou City was higher under equalised public health services. However, a need still exists to help the FP with low SES to improve their RH knowledge and skills through access to public RH services.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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