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Find video protocols related to scientific articles indexed in Pubmed.
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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Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B.
N. Engl. J. Med.
PUBLISHED: 11-20-2014
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Background In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity. Methods We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×10(12) vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. Results A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. Conclusions In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238 .).
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Asymmetric Hetero-Diels-Alder Reaction of Diazenes Catalyzed by Chiral Silver Phosphate: Water Participates in the Catalysis and Stereocontrol.
Org. Lett.
PUBLISHED: 11-20-2014
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The chiral silver phosphate was confirmed to efficiently catalyze a highly regio- and enantioselective hetero-Diels-Alder reaction of diazenes to furnish piperazine derivatives in high yields and excellent ee values. DFT calculations revealed that the water molecule participates in the catalysis by coordination to silver phosphate and also found that the hydroxy group of 1-hydroxy-2,3-hexadiene not only formed a hydrogen bond with the oxygen of phosphate but also coordinated to the Ag(I) to simultaneously stabilize the transition states and control the regioselectivity.
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Discovery and Characterization of the Tuberculosis Drug Lead Ecumicin.
Org. Lett.
PUBLISHED: 11-20-2014
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The new tuberculosis (TB) lead ecumicin (1), a cyclic tridecapeptide, was isolated from Nonomuraea sp. MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS(2). Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey's analysis.
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Flexible Single Crystal Silicon Nanomembrane Photonic Crystal Cavity.
ACS Nano
PUBLISHED: 11-20-2014
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Flexible inorganic electronic devices promise numerous applications, especially in fields that could not be covered satisfactorily by conventional rigid devices. Benefits on a similar scale are also foreseeable for silicon photonic components. However, the difficulty in transferring intricate silicon photonic devices has deterred widespread development. In this paper, we demonstrate a flexible single crystal silicon nanomembrane photonic crystal microcavity through a bonding and substrate removal approach. The transferred cavity shows a quality factor of 2.2×10^4, and could be bended to a curvature of 5 mm radius without deteriorating the performance compared to its counterparts on rigid substrates. A thorough characterization of the device reveals that the resonant wavelength is a linear function of the bending-induced strain. The device also shows a curvature-independent sensitivity to the ambient index variation.
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Composite 5A zeolite with ultrathin porous TiO2 coating for selective gas adsorption.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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A composite zeolite adsorbent was prepared by conformally depositing an ultrathin porous TiO2 coating on the external surface of the 5A zeolite by molecular layer deposition (MLD) and subsequent calcination. The composite adsorbent showed significantly improved ideal adsorption selectivity for CO2-CH4, CO2-N2 and propylene-propane.
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Why a Lotus-like Superhydrophobic Surface Is Self-Cleaning? An Explanation from Surface Force Measurements and Analysis.
Langmuir
PUBLISHED: 11-04-2014
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The unique self-cleaning feature of the lotus-like superhydrophobic (SH) surface attracted worldwide interest in recent years. However, the mechanism of the self-cleaning phenomena remains unclear. Here, we attempt to provide a comprehensive understanding of why self-cleaning of the particles with a broad range of size can be realized on the lotus-like SH surfaces. After measurements and analysis of the force involved at the interface, we conclude that there are four main preconditions for self-cleaning: (1) contact angle (CA) > 90°, (2) low enough sliding angle, (3) low enough adhesion force, and (4) proper particle size. However, as far as the lotus-like SH surface and typical dust are concerned, all the preconditions will be satisfied automatically. We also observe that the particles with a broad range of size (from submicron level to the millimeter level) and density (virtually no limit) can be driven by a water droplet on the lotus-like SH surface. This interesting finding may be helpful for the design of novel engineering system at the micron-millimeter scale in the future.
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Simian Hemorrhagic Fever Virus Cell Entry is Dependent on CD163 and Uses a Clathrin-mediated Endocytosis-like Pathway.
J. Virol.
PUBLISHED: 10-31-2014
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Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques, but is thought to be nonpathogenic for humans. To date, the SHFV lifecycle is almost completely uncharacterized on the molecular level. Here we describe the first steps of the SHFV lifecycle. Our experiments indicate that SHFV enters target cells by low pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-?-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin, and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knock-out study and electron-microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, ?-chymotrypsin, trypsin) abrogated entry, indicating that the SHFV cell-surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component.
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DNA methylation: the pivotal interaction between early-life nutrition and glucose metabolism in later life.
Br. J. Nutr.
PUBLISHED: 10-20-2014
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Traditionally, it has been widely acknowledged that genes together with adult lifestyle factors determine the risk of developing some metabolic diseases such as insulin resistance, obesity and diabetes mellitus in later life. However, there is now substantial evidence that prenatal and early-postnatal nutrition play a critical role in determining susceptibility to these diseases in later life. Maternal nutrition has historically been a key determinant for offspring health, and gestation is the critical time window that can affect the growth and development of offspring. The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that exposures during early life play a critical role in determining the risk of developing metabolic diseases in adulthood. Currently, there are substantial epidemiological studies and experimental animal models that have demonstrated that nutritional disturbances during the critical periods of early-life development can significantly have an impact on the predisposition to developing some metabolic diseases in later life. The hypothesis that epigenetic mechanisms may link imbalanced early-life nutrition with altered disease risk has been widely accepted in recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic processes play a significant role in regulating tissue-specific gene expression, and hence alterations in these processes may induce long-term changes in gene function and metabolism that persist throughout the life course. The present review focuses on how nutrition in early life can alter the epigenome, produce different phenotypes and alter disease susceptibilities, especially for impaired glucose metabolism.
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Antiphospholipid antibodies attenuate endothelial repair and promote neointima formation in mice.
J Am Heart Assoc
PUBLISHED: 10-16-2014
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Antiphospholipid syndrome patients have antiphospholipid antibodies (aPLs) that promote thrombosis, and they have increased cardiovascular disease risk. Although the basis for the thrombosis has been well delineated, it is not known why antiphospholipid syndrome patients also have an increased prevalence of nonthrombotic vascular occlusion. The aims of this work were to determine if aPLs directly promote medial hypertrophy or neointima formation in mice and to identify the underlying mechanisms.
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[Identification of prototype foamy virus Bel1 nuclear localization signal and its corresponding importins].
Bing Du Xue Bao
PUBLISHED: 10-03-2014
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Bel1, a transactivator of prototype foamy virus (PFV), plays pivotal roles in the replication of PFV. Previous studies have shown that Bel1 bears a nuclear localization signal (NLS), but its amino acid sequence remains unclear and the corresponding importins have not been identified. In this report, we inserted various fragments of Bel1 into an EGFP-GST fusion protein and investigated their subcellular localization by fluorescence microscopy. We found that the 215PRQKRPR221 fragment could direct nuclear localization, which accords with the consensus sequence K(K/R)X(K/R) of monopartite NLS. Point mutation experiments revealed that K218, R219, and R221 are essential for the nuclear localization of Bel1. The results of the GST-pulldown showed that the Bel1 fragment with residues 215-223, which bears the NLS, interacts with KPNA1, KPNA6, and KPNA7. This result suggests that KPNA1, KPNA6, and KPNA7 maybe involved in Bel1 nuclear translocation.
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Primary diffuse-type tenosynovial giant cell tumor of the spine: a report of 3 cases and systemic review of the literature.
Turk Neurosurg
PUBLISHED: 10-01-2014
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Three patients with spinal primary diffuse-type tenosynovial giant cell tumor (DTGCT) received surgical treatment in our department between 2002 and 2012. All 3 patients were female and aged 23, 33, and 44 years. The mean time from symptom onset to diagnosis was 17 months (range, 5-24 months). One case involved the C1 right lateral mass and C2 vertebral body, the second involved the C1-2 left lateral masses and C2 vertebral body, and the third involved the C5-7 left lateral mass and C6 vertebral body. All patients underwent computed tomographyguided biopsy to confirm the diagnosis of tenosynovial giant cell tumor. Gross total resection was achieved in all patients, including 2 piecemeal resections and 1 en-bloc resection. The mean follow-up time was 6 years (range, 1-11 years), and there was no sign of recurrence in the patients. Seventy cases have been identified so far in the English literature. The male to female ratio is 1:1.38. The mean patient age is 38.5 ± 17.9 years. The tumor distribution includes 32 cases in the cervical spine, 14 in the thoracic spine, 22 in the lumbar spine, and 1 in the sacrococcygeal region. The recurrence rate for patients who underwent gross total resection was 7.7%, and tumor progression was observed in 66.7% of patients who underwent subtotal resection. Above all, DTGCT is a rare primary spinal neoplasm. Preoperative image-guided biopsies play an important role in the diagnosis and treatment strategy. Gross total resection is the best treatment strategy and can reduce the recurrence rate.
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Catalyst-Controlled Stereoselective Olefin Metathesis as a Principal Strategy in Multistep Synthesis Design: A Concise Route to (+)-Neopeltolide.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 09-15-2014
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Molybdenum-, tungsten-, and ruthenium-based complexes that control the stereochemical outcome of olefin metathesis reactions have been recently introduced. However, the complementary nature of these systems through their combined use in multistep complex molecule synthesis has not been illustrated. A concise diastereo- and enantioselective route that furnishes the anti-proliferative natural product neopeltolide is now disclosed. Catalytic transformations are employed to address every stereochemical issue. Among the featured processes are an enantioselective ring-opening/cross-metathesis promoted by a Mo monoaryloxide pyrrolide (MAP) complex and a macrocyclic ring-closing metathesis that affords a trisubstituted alkene and is catalyzed by a Mo bis(aryloxide) species. Furthermore, Z-selective cross-metathesis reactions, facilitated by Mo and Ru complexes, have been employed in the stereoselective synthesis of the acyclic dienyl moiety of the target molecule.
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Evaluation of a new pediatric positive airway pressure mask.
J Clin Sleep Med
PUBLISHED: 09-15-2014
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The choice and variety of pediatric masks for continuous positive airway pressure (CPAP) is limited in the US. Therefore, clinicians often prescribe modified adult masks. Until recently a mask for children aged < 7 years was not available. This study evaluated apnea-hypopnea index (AHI) equivalence and acceptability of a new pediatric CPAP mask for children aged 2-7 years (Pixi; ResMed Ltd, Sydney, Australia).
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Application of a low cost array-based technique - TAB-Array - for quantifying and mapping both 5mC and 5hmC at single base resolution in human pluripotent stem cells.
Genomics
PUBLISHED: 08-29-2014
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5-hydroxymethylcytosine (5hmC), an oxidized derivative of 5-methylcytosine (5mC), has been implicated as an important epigenetic regulator of mammalian development. Current procedures use DNA sequencing methods to discriminate 5hmC from 5mC, limiting their accessibility to the scientific community. Here we report a method that combines TET-assisted bisulfite conversion with Illumina 450K DNA methylation arrays for a low-cost high-throughput approach that distinguishes 5hmC and 5mC signals at base resolution. Implementing this approach, termed "TAB-array", we assessed DNA methylation dynamics in the differentiation of human pluripotent stem cells into cardiovascular progenitors and neural precursor cells. With the ability to discriminate 5mC and 5hmC, we identified a large number of novel dynamically methylated genomic regions that are implicated in the development of these lineages. The increased resolution and accuracy afforded by this approach provides a powerful means to investigate the distinct contributions of 5mC and 5hmC in human development and disease.
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Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring.
Int J Mol Sci
PUBLISHED: 08-25-2014
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Maternal dietary modifications determine the susceptibility to metabolic diseases in adult life. However, whether maternal high-fat feeding can modulate glucose and lipid metabolism in the early life of offspring is less understood. Furthermore, we explored the underlying mechanisms that influence the phenotype. Using C57BL/6J mice, we examined the effects on the offspring at weaning from dams fed with a high-fat diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time PCR were performed in the liver tissues of the offspring mice. The offspring of the dams fed the high-fat diet had a heavier body weight, impaired glucose tolerance, decreased insulin sensitivity, increased serum cholesterol and hepatic steatosis at weaning. Bioinformatic analyses indicated that all differentially expressed genes of the offspring between the two groups were mapped to nine pathways. Genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway were verified by quantitative real-time PCR and these genes were significantly up-regulated in the high-fat diet offspring. A maternal high-fat diet during pregnancy and lactation can modulate hepatic glucose, lipid homeostasis, and gene expression in the PPAR signaling in the early life of offspring, and our results suggested that potential mechanisms that influences this phenotype may be related partially to up-regulate some gene expression in the PPAR signalling pathway.
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The Cap1-claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-25-2014
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The paracellular pathway through the tight junction provides an important route for transepithelial chloride reabsorption in the kidney, which regulates extracellular salt content and blood pressure. Defects in paracellular chloride reabsorption may in theory cause deregulation of blood pressure. However, there is no evidence to prove this theory or to demonstrate the in vivo role of the paracellular pathway in renal chloride handling. Here, using a tissue-specific KO approach, we have revealed a chloride transport pathway in the kidney that requires the tight junction molecule claudin-4. The collecting duct-specific claudin-4 KO animals developed hypotension, hypochloremia, and metabolic alkalosis due to profound renal wasting of chloride. The claudin-4-mediated chloride conductance can be regulated endogenously by a protease-channel-activating protease 1 (cap1). Mechanistically, cap1 regulates claudin-4 intercellular interaction and membrane stability. A putative cap1 cleavage site has been identified in the second extracellular loop of claudin-4, mutation of which abolished its regulation by cap1. The cap1 effects on paracellular chloride permeation can be extended to other proteases such as trypsin, suggesting a general mechanism may also exist for proteases to regulate the tight junction permeabilities. Together, we have discovered a theory that paracellular chloride permeability is physiologically regulated and essential to renal salt homeostasis and blood pressure control.
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Chordomas of the upper cervical spine: clinical characteristics and surgical management of a series of 21 patients.
Chin. Med. J.
PUBLISHED: 08-23-2014
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Chordomas of the upper cervical spine are rare and present unique surgical challenge. This study aimed to describe the clinical characteristics and surgical management of patients with chordomas of the upper cervical spine.
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Influenza A Virus Polymerase Is a Site for Adaptive Changes during Experimental Evolution in Bat Cells.
J. Virol.
PUBLISHED: 08-20-2014
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The recent identification of highly divergent influenza A viruses in bats revealed a new, geographically dispersed viral reservoir. To investigate the molecular mechanisms of host-restricted viral tropism and the potential for transmission of viruses between humans and bats, we exposed a panel of cell lines from bats of diverse species to a prototypical human-origin influenza A virus. All of the tested bat cell lines were susceptible to influenza A virus infection. Experimental evolution of human and avian-like viruses in bat cells resulted in efficient replication and created highly cytopathic variants. Deep sequencing of adapted human influenza A virus revealed a mutation in the PA polymerase subunit not previously described, M285K. Recombinant virus with the PA M285K mutation completely phenocopied the adapted virus. Adaptation of an avian virus-like virus resulted in the canonical PB2 E627K mutation that is required for efficient replication in other mammals. None of the adaptive mutations occurred in the gene for viral hemagglutinin, a gene that frequently acquires changes to recognize host-specific variations in sialic acid receptors. We showed that human influenza A virus uses canonical sialic acid receptors to infect bat cells, even though bat influenza A viruses do not appear to use these receptors for virus entry. Our results demonstrate that bats are unique hosts that select for both a novel mutation and a well-known adaptive mutation in the viral polymerase to support replication.
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A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep apnea associated with chronic use of opioids.
J Clin Sleep Med
PUBLISHED: 08-15-2014
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To compare the efficacy and patient comfort of a new mode of minute ventilation-targeted adaptive servoventilation (ASVAuto) with auto-titrating expiratory positive airway pressure (EPAP) versus bilevel with back-up respiratory rate (bilevel-ST) in patients with central sleep apnea (CSA) associated with chronic use of opioid medications.
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Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway.
PLoS ONE
PUBLISHED: 08-11-2014
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In daily life, humans are exposed to the extremely low-frequency electromagnetic fields (ELF-EMFs) generated by electric appliances, and public concern is increasing regarding the biological effects of such exposure. Numerous studies have yielded inconsistent results regarding the biological effects of ELF-EMF exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, inhibiting cell proliferation. To present well-founded results, we comprehensively evaluated the biological effects of ELF-EMFs at the transcriptional, protein, and cellular levels. Human HaCaT cells from an immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation. Protein expression experiments revealed that ELF-EMFs induced the activation of the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of cell cycle progression at G1 and G2/M, exhibited a higher level of expression in exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF-EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes checkpoint kinase 2; Chk2) was suppressed by specific small interfering RNA (siRNA). These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the precise control of the ELF-EMF exposure and rigorous sham-exposure experiments, all transcriptional, protein, and cellular level experiments consistently supported the conclusion. This is the first study to confirm that a specific pathway is triggered by ELF-EMF exposure.
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Treatment of Multiple Aneurysms.
Ann Vasc Surg
PUBLISHED: 08-07-2014
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This study presented a rare case of fast-growing multiple aneurysms. A male patient rapidly developed multiple aneurysms involving the aortic arch and the carotid, internal iliac, right femoral, and left popliteal arteries over a period of 2 months, accompanied by fever, hyperfibrinogenemia, thrombocythemia, and folliculitis-like skin lesions. He underwent aneurysmectomy and revascularization of the left popliteal artery, stent implantation in the right superficial femoral artery, and local repair of the tibioperoneal trunk artery. An 18-month follow-up showed that his condition was controlled by anticoagulation and immunosuppressive therapy. Despite the effective treatment of his disease, the exact cause was not established.
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Sleep Apnea and the Risk of Chronic Kidney Disease: A Nationwide Population-Based Cohort Study.
Sleep
PUBLISHED: 08-06-2014
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Sleep apnea (SA) is characterized by apnea during sleep and is associated with cardiovascular diseases and an increase in all-cause mortality. Chronic kidney disease (CKD) is a global health problem that has placed a substantial burden on healthcare resources. However, the relationship between SA and the incidence of CKD is not clear. This study aimed to determine whether SA is an independent risk factor for the development of CKD.
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Reduced signaling of PI3K-Akt and RAS-MAPK pathways is the key target for weight-loss-induced cancer prevention by dietary calorie restriction and/or physical activity.
J. Nutr. Biochem.
PUBLISHED: 07-25-2014
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Weight control through either dietary calorie restriction (DCR) or exercise has been associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics using genomics, proteomics and lipidomics was employed to elucidate the molecular targets of weight control in a mouse skin cancer model. SENCAR mice were randomly assigned into four groups for 10 weeks: ad-libitum-fed sedentary control, ad-libitum-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE) and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67 and 110 genes were significantly changed in DCR, PE and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE but not AE as measured through GenMAPP software. Proteomics analysis identified ~120 proteins, with 27 proteins significantly changed by DCR, including up-regulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although a full impact has not been determined yet, it appears that the reduction of both Ras-MAPK and PI3K-Akt signaling pathways is a cancer preventive target that has been consistently demonstrated by three bioinformatics approaches.
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Tuning the underwater oleophobicity of graphene oxide coatings via UV irradiation.
Chem. Commun. (Camb.)
PUBLISHED: 07-16-2014
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Ultraviolet (UV) irradiation was utilized to gradually modify the chemistry and structure of graphene oxide (GO) flakes, as confirmed by XPS and AFM. Ultrathin GO coatings/membranes, made of UV-irradiated flakes, showed tunable underwater oleophobicity. UV-treated, superoleophobic GO membranes exhibited excellent antifouling capability for oil/water separation.
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Correlation of high-molecular-weight adiponectin and leptin concentrations with anthropometric parameters and insulin sensitivity in newborns.
Int J Endocrinol
PUBLISHED: 07-08-2014
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Objective. High-molecular-weight adiponectin (HMW-adiponectin) and leptin are two important adipokines. The aim of this study was to examine the association between the two adipokines and anthropometric measurements of neonates at birth. Furthermore, we would like to explore whether HMW-adiponectin and leptin correlate with insulin sensitivity in neonates. Methods. Venous cord blood samples were obtained from 266 full-term healthy neonates consecutively born at Peking Union Medical College Hospital. HMW-adiponectin, leptin, blood glucose, and insulin concentrations were measured. Results. HMW-adiponectin and leptin were significantly higher in females compared with males (P = 0.031 and P = 0.000, resp.). Univariate correlation analysis showed that leptin concentrations in cord blood were positively associated with gestational age, birth weight, body length, ponderal index, placenta weight, insulin, and insulin sensitivity (all P < 0.001). However, there was no correlation between cord blood HMW-adiponectin levels and foetal anthropometric measurements or foetal insulin sensitivity indicators (all P > 0.05). Multivariate linear regression analysis indicated that leptin (B = -0.126, P = 0.045) in cord blood was independently associated with insulin sensitivity. Conclusions. Leptin concentrations, but not HMW-adiponectin, were positively associated with foetal anthropometric measurements. Leptin concentrations are significantly associated with foetal insulin sensitivity, and there were no significant correlations between HMW-adiponectin levels and foetal insulin sensitivity.
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Formation of white oxide layer on Zr-14Nb alloy using thermal treatment.
Dent Mater J
PUBLISHED: 07-02-2014
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This study aimed to develop a novel abutment material with good esthetic and mechanical properties by producing a white oxide layer on a zirconium-14 mass% niobium (Zr-14Nb) alloy substrate using a thermal oxidation process. Oxidation temperatures ranged 700-1000°C and oxidation time ranged 30-180 min. The color of the oxide layer varied depending on temperature and time. A white oxide layer was obtained under appropriate conditions. The oxide layer thickness increased with increased temperature and time, as revealed by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Moreover, X-ray diffraction and X-ray photoelectron spectroscopy revealed that the oxide layer was predominantly monoclinic ZrO2, tetragonal ZrO2, and Nb2O5. The oxide layer revealed good abrasion resistance and high adhesion to the substrate. This novel process for producing white materials with good mechanical properties will be useful for abutments and prostheses in dental implant treatment.
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Determination of Saponins and Flavonoids in Ivy Leaf Extracts Using HPLC-DAD.
J Chromatogr Sci
PUBLISHED: 07-02-2014
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A new method for the determination of six compounds, chlorogenic acid, rutin, nicotiflorin, hederacoside C, hederasaponin B and ?-hederin, in ivy leaf extracts using high-performance liquid chromatography with diode array detector was developed. The chromatographic separation was performed on a YMC Hydrosphere C18 analytical column using a gradient elution of 0.1% phosphoric acid and acetonitrile. The method was validated in terms of specificity, linearity (r(2) > 0.9999), precision [relative standard deviation (RSD) < 0.36%] and accuracy (97.4-103.8%). The limit of detection and limit of quantification were <20.32 and 61.56 ng for all analytes, respectively. The tested compounds were found to be stable in the ivy leaf extract from 0 to 48 h, and the RSD value for each compound was <0.90%. The validated method was successfully applied to quantify all six compounds in a 30% ethanol ivy leaf extract and 13 ivy leaf extract products. The results showed that all the tested products satisfied the minimum requirement for the content of hederacoside C. However, there were some differences between the contents of other constituents.
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[3+3] annulation of allylic phosphoryl-stabilized carbanions/phosphorus ylides and vinyl azides: a practice strategy for synthesis of polyfunctionalized anilines.
Chem. Commun. (Camb.)
PUBLISHED: 06-24-2014
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Tandem Michael addition and Witting or Horner-Wadsworth-Emmons olefination initiated [3+3] annulation between vinyl azides and allylic phosphorus ylides or allylic phosphoryl-stabilized carbanions has been developed. This one-pot protocol furnishes highly functionalized anilines in good to excellent yields under mild, room-temperature conditions. A rational mechanism is also proposed.
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The prevention of titanium-particle-induced osteolysis by OA-14 through the suppression of the p38 signaling pathway and inhibition of osteoclastogenesis.
Biomaterials
PUBLISHED: 05-21-2014
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Wear-particle-induced osteolysis leads to prosthesis loosening, which is one of the most common causes of joint-implant failure, a problem that must be fixed using revision surgery. Thus, a potential treatment for prosthetic loosening is focused on inhibiting osteoclastic bone resorption, which prevents wear-particle-induced osteolysis. In this study, we synthesized a compound named OA-14 (N-(3- (dodecylcarbamoyl)phenyl)-1H-indole-2-carboxamide) and examined how OA-14 affects titanium (Ti)-particle-induced osteolysis and osteoclastogenesis. We report that OA-14 treatment protected against Ti-particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of tartrate-resistant acid phosphatase-positive osteoclasts decreased after treatment with OA-14 in vivo, which suggested that OA-14 inhibits osteoclast formation. To test this hypothesis, we conducted in vitro studies, and our results revealed that OA-14 markedly diminished osteoclast differentiation and osteoclast-specific gene expression in a dose- and time-dependent manner. Moreover, OA-14 suppressed osteoclastic bone resorption and F-actin ring formation. Furthermore, we determined that OA-14 inhibited osteoclastogenesis by specifically blocking the p38-Mitf-c-fos-NFATc1 signaling cascade induced by RANKL (ligand of receptor activator of nuclear factor ?B). Collectively, our results suggest that the compound OA-14 can be safely used for treating particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.
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Enhanced acoustic sensing through wave compression and pressure amplification in anisotropic metamaterials.
Nat Commun
PUBLISHED: 04-14-2014
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Acoustic sensors play an important role in many areas, such as homeland security, navigation, communication, health care and industry. However, the fundamental pressure detection limit hinders the performance of current acoustic sensing technologies. Here, through analytical, numerical and experimental studies, we show that anisotropic acoustic metamaterials can be designed to have strong wave compression effect that renders direct amplification of pressure fields in metamaterials. This enables a sensing mechanism that can help overcome the detection limit of conventional acoustic sensing systems. We further demonstrate a metamaterial-enhanced acoustic sensing system that achieves more than 20?dB signal-to-noise enhancement (over an order of magnitude enhancement in detection limit). With this system, weak acoustic pulse signals overwhelmed by the noise are successfully recovered. This work opens up new vistas for the development of metamaterial-based acoustic sensors with improved performance and functionalities that are highly desirable for many applications.
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Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer.
BMC Genomics
PUBLISHED: 04-04-2014
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Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments.
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Cystatin C as a Predictor for Outcomes in Patients with Negligible Renal Function.
Blood Purif.
PUBLISHED: 04-03-2014
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Background: High serum cystatin C (CysC) has been associated with clinical risks independently of the glomerular filtration rate (GFR). This study aims to investigate the predictive power of CysC in patients with a negligible GFR. Methods: Patients on chronic hemodialysis or peritoneal dialysis were enrolled for measurement of CysC levels and were followed up for one year. A daily urine amount <100 ml was considered negligible residual renal function (RRF). Results: CysC results were available in 183 dialysis patients. Of these, 131 patients had a negligible RRF. The multivariate Cox proportional hazards model showed that CysC was an independent predictor of fatal and nonfatal cardiovascular and infection events in all dialysis patients and in dialysis patients with a negligible RRF. Conclusion: CysC maintained its predictive power for adverse outcomes in patients with no meaningful GFR, indicating that the prognostic value of CysC is independent of the GFR. © 2014 S. Karger AG, Basel.
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Bortezomib for chronic relapsing thrombotic thrombocytopenic purpura: a case report.
Transfusion
PUBLISHED: 03-24-2014
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Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterized by a severe deficiency of ADAMTS13 activity. Although therapeutic plasma exchange (PLEX) is the standard of care, 30% to 50% patients develop exacerbation or relapse, requiring immunomodulatory agents. Of these agents, glucocorticoids, rituximab, and cyclosporine?A are the most frequently used.
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Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells.
BMC Nephrol
PUBLISHED: 02-14-2014
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Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored.
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ABRO1 suppresses tumourigenesis and regulates the DNA damage response by stabilizing p53.
Nat Commun
PUBLISHED: 02-04-2014
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Abraxas brother 1 (ABRO1) has been reported to be a component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin. However, current knowledge of the functions of ABRO1 is limited. Here we report that ABRO1 is frequently downregulated in human liver, kidney, breast and thyroid gland tumour tissues. Depletion of ABRO1 in cancer cells reduces p53 levels and enhances clone formation and cellular transformation. Conversely, overexpression of ABRO1 suppresses cell proliferation and tumour formation in a p53-dependent manner. We further show that ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7. DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus, and the induction of p53 by DNA damage is almost completely attenuated by ABRO1 depletion. Our study shows that ABRO1 is a novel p53 regulator that plays an important role in tumour suppression and the DNA damage response.
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Risk factors of sensitization to human leukocyte antigen in end-stage renal disease patients.
Hum. Immunol.
PUBLISHED: 02-04-2014
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Pre-sensitization to human leukocyte antigen (HLA) is closely related to the prognosis of renal transplantation. Concerning the risk factors for HLA sensitization, most studies focused only on selected transplant candidates.
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Residues R(199)H(200) of prototype foamy virus transactivator Bel1 contribute to its binding with LTR and IP promoters but not its nuclear localization.
Virology
PUBLISHED: 01-15-2014
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Prototype foamy virus encodes a transactivator called Bel1 that enhances viral gene transcription and is essential for PFV replication. Nuclear localization of Bel1 has been reported to rely on two proximal basic motifs R(199)H(200) and R(221)R(222)R(223) that likely function together as a bipartite nuclear localization signal. In this study, we report that mutating R(221)R(222)R(223), but not R(199)H(200), relocates Bel1 from the nucleus to the cytoplasm, suggesting an essential role for R(221)R(222)R(223) in the nuclear localization of Bel1. Although not affecting the nuclear localization of Bel1, mutating R(199)H(200) disables Bel1 from transactivating PFV promoters. Results of EMSA reveal that the R(199)H(200) residues are vital for the binding of Bel1 to viral promoter DNA. Moreover, mutating R(199)H(200) in Bel1 impairs PFV replication to a much greater extent than mutating R(221)R(222)R(223). Collectively, our findings suggest that R(199)H(200) directly participate in Bel1 binding to viral promoter DNA and are indispensible for Bel1 transactivation activity.
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Light trapping and surface plasmon enhanced high-performance NIR photodetector.
Sci Rep
PUBLISHED: 01-13-2014
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Heterojunctions near infrared (NIR) photodetectors have attracted increasing research interests for their wide-ranging applications in many areas such as military surveillance, target detection, and light vision. A high-performance NIR light photodetector was fabricated by coating the methyl-group terminated Si nanowire array with plasmonic gold nanoparticles (AuNPs) decorated graphene film. Theoretical simulation based on finite element method (FEM) reveals that the AuNPs@graphene/CH3-SiNWs array device is capable of trapping the incident NIR light into the SiNWs array through SPP excitation and coupling in the AuNPs decorated graphene layer. What is more, the coupling and trapping of freely propagating plane waves from free space into the nanostructures, and surface passivation contribute to the high on-off ratio as well.
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SMART DOCS: A New Patient-Centered Outcomes and Coordinated-Care Management Approach for the Future Practice of Sleep Medicine.
Sleep
PUBLISHED: 01-07-2014
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The practice of medicine is currently undergoing a transformation to become more efficient, cost-effective, and patient centered in its delivery of care. The aim of this article is to stimulate discussion within the sleep medicine community in addressing these needs by our approach as well as other approaches to sleep medicine care. The primary goals of the Sustainable Methods, Algorithms, and Research Tools for Delivering Optimal Care Study (SMART DOCS) are: (1) to introduce a new Patient-Centered Outcomes and Coordinated-Care Management (PCCM) approach for the future practice of sleep medicine, and (2) to test the PCCM approach against a Conventional Diagnostic and Treatment Outpatient Medical Care (CONV) approach in a randomized, two-arm, single-center, long-term, comparative effectiveness trial. The PCCM approach is integrated into a novel outpatient care delivery model for patients with sleep disorders that includes the latest technology, allowing providers to obtain more accurate and rapid diagnoses and to make evidence-based treatment recommendations, while simultaneously enabling patients to have access to personalized medical information and reports regarding their diagnosis and treatment so that they can make more informed health care decisions. Additionally, the PCCM approach facilitates better communication between patients, referring primary care physicians, sleep specialists, and allied health professionals so that providers can better assist patients in achieving their preferred outcomes. A total of 1,506 patients 18 y or older will be randomized to either the PCCM or CONV approach and will be followed for at least 1 y with endpoints of improved health care performance, better health, and cost control.
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Carbohydrate antigens as potential biomarkers for the malignancy in patients with idiopathic deep venous thrombosis: A retrospective cohort study.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 01-06-2014
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A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, ?2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (?-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and ?2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and ?2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.
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Haemolytic uremic syndrome following fire ant bites.
BMC Nephrol
PUBLISHED: 01-06-2014
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Haemolytic-uremic syndrome (HUS) is a severe, life-threatening disease with symptoms such as haemolytic anaemia, renal failure, and a low platelet count. Possible aetiology includes bacterial infections, medication, post-hematopoietic cell transplantation, pregnancy, autoimmune disease, and acquired immunodeficiency syndrome.
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Fibrinogen Dusart presenting as recurrent thromboses in the hepatic portal system.
Blood Coagul. Fibrinolysis
PUBLISHED: 01-04-2014
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Dysfibrogenemias are characterized by the production of abnormally functioning fibrinogen, occurring in the presence of liver disease, medication toxicity, malignancy, or genetic mutation. Here, we report a patient with multiple, separate episodes of hepatic portal system thromboses associated with dysfibrinogenemia. Molecular studies identified the presence of a 554Arg?Cys mutation in the fibrinogen A? gene, previously identified as Fibrinogen Dusart (also known as Fibrinogen Paris V and Fibrinogen Chapel Hill). This case further illustrates the association of this dysfibrinogenemia with a unique thrombophilic manifestation.
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Distinct Epidermal Keratinocytes Respond to Extremely Low-Frequency Electromagnetic Fields Differently.
PLoS ONE
PUBLISHED: 01-01-2014
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Following an increase in the use of electric appliances that can generate 50 or 60 Hz electromagnetic fields, concerns have intensified regarding the biological effects of extremely low-frequency electromagnetic fields (ELF-EMFs) on human health. Previous epidemiological studies have suggested the carcinogenic potential of environmental exposure to ELF-EMFs, specifically at 50 or 60 Hz. However, the biological mechanism facilitating the effects of ELF-EMFs remains unclear. Cellular studies have yielded inconsistent results regarding the biological effects of ELF-EMFs. The inconsistent results might have been due to diverse cell types. In our previous study, we indicated that 1.5 mT, 60 Hz ELF-EMFs will cause G1 arrest through the activation of the ATM-Chk2-p21 pathway in human keratinocyte HaCaT cells. The aim of the current study was to investigate whether ELF-EMFs cause similar effects in a distinct epidermal keratinocyte, primary normal human epidermal keratinocytes (NHEK), by using the same ELF-EMF exposure system and experimental design. We observed that ELF-EMFs exerted no effects on cell growth, cell proliferation, cell cycle distribution, and the activation of ATM signaling pathway in NHEK cells. We demonstrated that the 2 epidermal keratinocytes responded to ELF-EMFs differently. To further validate this finding, we simultaneously exposed the NHEK and HaCaT cells to ELF-EMFs in the same incubator for 168 h and observed the cell growths. The simultaneous exposure of the two cell types results showed that the NHEK and HaCaT cells exhibited distinct responses to ELF-EMFs. Thus, we confirmed that the biological effects of ELF-EMFs in epidermal keratinocytes are cell type specific. Our findings may partially explain the inconsistent results of previous studies when comparing results across various experimental models.
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CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection.
PLoS ONE
PUBLISHED: 01-01-2014
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Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.
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Processing Deficits of Motion of Contrast-Modulated Gratings in Anisometropic Amblyopia.
PLoS ONE
PUBLISHED: 01-01-2014
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Several studies have indicated substantial processing deficits for static second-order stimuli in amblyopia. However, less is known about the perception of second-order moving gratings. To investigate this issue, we measured the contrast sensitivity for second-order (contrast-modulated) moving gratings in seven anisometropic amblyopes and ten normal controls. The measurements were performed with non-equated carriers and a series of equated carriers. For comparison, the sensitivity for first-order motion and static second-order stimuli was also measured. Most of the amblyopic eyes (AEs) showed reduced sensitivity for second-order moving gratings relative to their non-amblyopic eyes (NAEs) and the dominant eyes (CEs) of normal control subjects, even when the detectability of the noise carriers was carefully controlled, suggesting substantial processing deficits of motion of contrast-modulated gratings in anisometropic amblyopia. In contrast, the non-amblyopic eyes of the anisometropic amblyopes were relatively spared. As a group, NAEs showed statistically comparable performance to CEs. We also found that contrast sensitivity for static second-order stimuli was strongly impaired in AEs and part of the NAEs of anisometropic amblyopes, consistent with previous studies. In addition, some amblyopes showed impaired performance in perception of static second-order stimuli but not in that of second-order moving gratings. These results may suggest a dissociation between the processing of static and moving second-order gratings in anisometropic amblyopia.
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Evaluation of Gridded Precipitation Data for Driving SWAT Model in Area Upstream of Three Gorges Reservoir.
PLoS ONE
PUBLISHED: 01-01-2014
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Gridded precipitation data are becoming an important source for driving hydrologic models to achieve stable and valid simulation results in different regions. Thus, evaluating different sources of precipitation data is important for improving the applicability of gridded data. In this study, we used three gridded rainfall datasets: 1) National Centers for Environmental Prediction - Climate Forecast System Reanalysis (NCEP-CFSR); 2) Asian Precipitation - Highly-Resolved Observational Data Integration Towards Evaluation (APHRODITE); and 3) China trend - surface reanalysis (trend surface) data. These are compared with monitoring precipitation data for driving the Soil and Water Assessment Tool in two basins upstream of Three Gorges Reservoir (TGR) in China. The results of one test basin with significant topographic influence indicates that all the gridded data have poor abilities in reproducing hydrologic processes with the topographic influence on precipitation quantity and distribution. However, in a relatively flat test basin, the APHRODITE and trend surface data can give stable and desirable results. The results of this study suggest that precipitation data for future applications should be considered comprehensively in the TGR area, including the influence of data density and topography.
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Evaluation of Outbreak Detection Performance Using Multi-Stream Syndromic Surveillance for Influenza-Like Illness in Rural Hubei Province, China: A Temporal Simulation Model Based on Healthcare-Seeking Behaviors.
PLoS ONE
PUBLISHED: 01-01-2014
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Syndromic surveillance promotes the early detection of diseases outbreaks. Although syndromic surveillance has increased in developing countries, performance on outbreak detection, particularly in cases of multi-stream surveillance, has scarcely been evaluated in rural areas.
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Adipose stem cells promote smooth muscle cells to secrete elastin in rat abdominal aortic aneurysm.
PLoS ONE
PUBLISHED: 01-01-2014
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Abdominal aortic aneurysm (AAA) is a life-threatening disease and its prevalence rate increases with social aging. The degradation of elastic is an important factor in the formation of AAA.
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Visualized gene network reveals the novel target transcripts Sox2 and Pax6 of neuronal development in trans-placental exposure to bisphenol A.
PLoS ONE
PUBLISHED: 01-01-2014
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Bisphenol A (BPA) is a ubiquitous endocrine disrupting chemical in our daily life, and its health effect in response to prenatal exposure is still controversial. Early-life BPA exposure may impact brain development and contribute to childhood neurological disorders. The aim of the present study was to investigate molecular target genes of neuronal development in trans-placental exposure to BPA.
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Influences of climate change on water resources availability in Jinjiang Basin, China.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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The influences of climate change on water resources availability in Jinjiang Basin, China, were assessed using the Block-wise use of the TOPmodel with the Muskingum-Cunge routing method (BTOPMC) distributed hydrological model. The ensemble average of downscaled output from sixteen GCMs (General Circulation Models) for A1B emission scenario (medium CO2 emission) in the 2050s was adopted to build regional climate change scenario. The projected precipitation and temperature data were used to drive BTOPMC for predicting hydrological changes in the 2050s. Results show that evapotranspiration will increase in most time of a year. Runoff in summer to early autumn exhibits an increasing trend, while in the rest period of a year it shows a decreasing trend, especially in spring season. From the viewpoint of water resource availability, it is indicated that it has the possibility that water resources may not be sufficient to fulfill irrigation water demand in the spring season and one possible solution is to store more water in the reservoir in previous summer.
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Estimating the occurrence of wind-driven coastal upwelling associated with "Aoshio" on the northeast shore of Tokyo Bay, Japan: an analytical model.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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"Aoshio" in Tokyo Bay is a hydroenvironmental phenomenon in which seawater appears milky blue due to reflection of sunshine off surface water which contains lots of sulfur particles. Its appearance is due to coastal upwelling of bottom oxygen-depleted water, which causes many deaths of shellfish and other aquatic animals around the bay. In this study, we derived some analytical solutions in the context of a two-layered fluid and used them to make a simple analytical model to estimate the occurrence of "Aoshio" phenomenon on the northeast shore of Tokyo Bay. Comparison with observation data suggested that this model was valid to a certain degree.
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Maternal arsenic exposure and DNA damage biomarkers, and the associations with birth outcomes in a general population from Taiwan.
PLoS ONE
PUBLISHED: 01-01-2014
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Inorganic arsenic (iAs) is an established transplacental agent known to affect fetal development in animal studies. However, iAs has not been adequately studied in the general population with respect to iAs exposure during pregnancy and its impact on the health status of newborns. The aims of this study were to 1) elucidate the association between arsenic exposure and oxidative/methylated DNA damage in pregnant women, and 2) determine the association with birth outcomes. A birth cohort study of 299 pregnant mother-newborn pairs was recruited during 2001-2002 in Taiwan. We collected maternal urine samples during the 3(rd) trimester for measuring iAs and its metabolites. We used high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for quantifications of the arsenic species. Liquid chromatography/tandem mass spectrometer (LC-MS/MS) was used to measure the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and N(7)-methylguanosine (N(7)-MeG) DNA damage biomarkers. Birth outcomes were collected to assess the associations with maternal arsenic exposure and the DNA damage biomarkers. Multiple regression analyses showed that maternal urinary iAs had positive associations with the methylated N(7)-MeG (beta?=?0.35, p<0.001) and oxidative 8-oxodG (beta?=?0.24, p<0.001) DNA damage biomarkers, and a decreased one-minute (1-min) Apgar score (beta?=?-0.23, p?=?0.041). Maternal N(7)-MeG was also associated with a decreased 1-min Apgar score (beta?=?-0.25, p?=?0.042). Mutual adjustment for iAs and N(7)-MeG showed an independent and significant prediction for a decreased 1-min Apgar score of iAs (beta?=?-0.28, p?=?0.036). Maternal iAs exposure was associated with both maternal DNA damage and adverse newborn health. Maternal N(7)-MeG levels might be a novel biomarker for monitoring fetal health related to iAs.
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Libraries from Libraries: A Series of Sulfonamide Linked Heterocycles Derived from the Same Scaffold.
Tetrahedron Lett.
PUBLISHED: 12-24-2013
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A libraries from libraries approach is described for the synthesis of five different sulfonamide linked scaffolds. Four of the scaffolds are sulfonamides linked to heterocycles; piperazine, thiourea, cyclic guanidine, and dimethyl cyclic guanidine. The fifth scaffold is a polyamine linked sulfonamide. Three different diversity positions were effectively incorporated into each scaffold providing a number of different compounds with good yields and purity.
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[Medical therapy of polyostotic fibrous dysplasia of the spinal column].
Beijing Da Xue Xue Bao
PUBLISHED: 12-18-2013
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To discuss treatments of spinal polyostotic fibrous dysplasia (PFD) and their clinical outcomes.
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[Efficacy of postoperative simple chemotherapy and concurrent chemoradiotherapy in FIGO stage IB2-IIB cervical cancer].
Beijing Da Xue Xue Bao
PUBLISHED: 12-18-2013
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To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer.
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Scaffold Ranking and Positional Scanning Utilized in the Discovery of nAChR-Selective Compounds Suitable for Optimization Studies.
J. Med. Chem.
PUBLISHED: 12-12-2013
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Nicotine binds to nicotinic acetylcholine receptors (nAChR), which can exist as many different subtypes. The ?4?2 nAChR is the most prevalent subtype in the brain and possesses the most evidence linking it to nicotine seeking behavior. Herein we report the use of mixture based combinatorial libraries for the rapid discovery of a series of ?4?2 nAChR selective compounds. Further chemistry optimization provided compound 301, which was characterized as a selective ?4?2 nAChR antagonist. This compound displayed no agonist activity but blocked nicotine-induced depolarization of HEK cells with an IC50 of approximately 430 nM. 301 demonstrated nearly 500-fold selectivity for binding and 40-fold functional selectivity for ?4?2 over ?3?4 nAChR. In total over 5 million compounds were assessed through the use of just 170 samples in order to identify a series of structural analogues suitable for future optimization toward the goal of developing clinically relevant smoking cessation medications.
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One-Pot Three-Component Approach to the Synthesis of Polyfunctional Pyrazoles.
Org. Lett.
PUBLISHED: 11-20-2013
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A simple, multicomponent, and straightforward reaction of vinyl azide, aldehyde, and tosylhydrazine affords the construction of 3,4,5-trisubstituted 1H-pyrazoles regioselectively in the presence of base with moderate to excellent yields. A range of functionality could be tolerated in this methodology, and a possible mechanism is proposed.
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An online one class support vector machine-based person-specific fall detection system for monitoring an elderly individual in a room environment.
IEEE J Biomed Health Inform
PUBLISHED: 11-19-2013
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In this paper, we propose a novel computer vision-based fall detection system for monitoring an elderly person in a home care, assistive living application. Initially, a single camera covering the full view of the room environment is used for the video recording of an elderly persons daily activities for a certain time period. The recorded video is then manually segmented into short video clips containing normal postures, which are used to compose the normal dataset. We use the codebook background subtraction technique to extract the human body silhouettes from the video clips in the normal dataset and information from ellipse fitting and shape description, together with position information, is used to provide features to describe the extracted posture silhouettes. The features are collected and an online one class support vector machine (OCSVM) method is applied to find the region in feature space to distinguish normal daily postures and abnormal postures such as falls. The resultant OCSVM model can also be updated by using the online scheme to adapt to new emerging normal postures and certain rules are added to reduce false alarm rate and thereby improve fall detection performance. From the comprehensive experimental evaluations on datasets for 12 people, we confirm that our proposed person-specific fall detection system can achieve excellent fall detection performance with 100% fall detection rate and only 3% false detection rate with the optimally tuned parameters. This work is a semiunsupervised fall detection system from a system perspective because although an unsupervised-type algorithm (OCSVM) is applied, human intervention is needed for segmenting and selecting of video clips containing normal postures. As such, our research represents a step toward a complete unsupervised fall detection system.
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Metabolites of 2,4,4-Tribrominated Diphenyl Ether (BDE-28) in Pumpkin after In Vivo and In Vitro Exposure.
Environ. Sci. Technol.
PUBLISHED: 11-18-2013
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There is currently limited knowledge on PBDE metabolism in plants although they could play an important role in the environmental transformation of these persistent organic pollutants. In this study, pumpkin (Cucurbita maxima × C. moschata) was chosen as the model to understand the fate of BDE-28 in plants. MeO-tri-BDEs, OH-tri-BDEs, and OH-tri-BDEs were found as metabolites in plant samples of both in vivo hydroponic and in vitro tissue culture exposure. Three MeO-tri-BDEs were further identified as para-substituted metabolites. MeO-BDEs and OH-BDEs, respectively, accounted for about 1.6% and 1.5% (recovery corrected) of initial amount of BDE-28 according to the semiquantitative results. Other PBDEs, especially less brominated PBDEs as impurities in the standard of BDE-28, were also detected. The impurities and evaporation of the standard must be considered when trace metabolites are studied in exposure experiments.
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A METTL3-METTL14 complex mediates mammalian nuclear RNA N(6)-adenosine methylation.
Nat. Chem. Biol.
PUBLISHED: 11-08-2013
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N(6)-methyladenosine (m(6)A) is the most prevalent and reversible internal modification in mammalian messenger and noncoding RNAs. We report here that human methyltransferase-like 14 (METTL14) catalyzes m(6)A RNA methylation. Together with METTL3, the only previously known m(6)A methyltransferase, these two proteins form a stable heterodimer core complex of METTL3-METTL14 that functions in cellular m(6)A deposition on mammalian nuclear RNAs. WTAP, a mammalian splicing factor, can interact with this complex and affect this methylation.
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[Research progress of decellularization and application in tissue engineering].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 11-01-2013
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To review the decellularized methods for obtaining extracellular matrix (ECM) and the applications of decellularized ECM scaffold in tissue engineering.
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Generation of insulin-producing cells from rat mesenchymal stem cells using an aminopyrrole derivative XW4.4.
Chem. Biol. Interact.
PUBLISHED: 10-28-2013
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Type 1 diabetes mellitus (T1DM), a multisystem disease with both biochemical and anatomical/structural consequences, is a major health concern worldwide. Pancreatic islet transplantation provides a promising treatment for T1DM. However, the limited availability of islet tissue or new sources of insulin producing cells (IPCs) that are responsive to glucose hinder this promising approach. Though slow, the development of pancreatic beta-cell lines from rodent or human origin has been steadily progressing. Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, culture-expanded, non-hematopoietic cells that are currently being investigated as a novel cellular therapy. The in vitro differentiation potential of IPCs has raised hopes for a treatment of clinical diseases associated with autoimmunity. We screened for small molecules that induce pancreatic differentiation of IPCs. There are some compounds which showed positive effects on the DTZ staining. The aminopyrrole derivative compound XW4.4 which shows the best activity among them was found to induce pancreatic differentiation of rat MSCs (rMSCs). The in vitro studies indicated that treatment of rMSCs with compound XW4.4 resulted in differentiated cells with characteristics of IPCs including islet-like clusters, spherical, grape-like morphology, insulin secretion, positive for dithizone, glucose stimulation and expression of pancreatic endocrine cell marker genes. The data has also suggested that hepatocyte nuclear factor 3? (HNF 3?) may be involved in pancreatic differentiation of rMSCs when treated with XW4.4. Results indicate that XW4.4 induced rMSCs support the efforts to derive functional IPCs and serve as a means to alleviate limitations surrounding islet cell transplantation in the treatment of T1DM.
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Effect of Remote Ischemic Preconditioning in the Elderly Patients With Coronary Artery Disease With Diabetes Mellitus Undergoing Elective Drug-Eluting Stent Implantation.
Angiology
PUBLISHED: 10-24-2013
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There is conflicting evidence regarding the effectiveness of remote ischemic preconditioning (RIPC) in patients undergoing elective percutaneous coronary intervention (PCI). Therefore, we prospectively enrolled elderly patients with coronary heart disease (CHD) with diabetes mellitus (DM) undergoing elective drug-eluting stent (DES) implantation. They were randomized to receive RIPC within 2 hours before PCI (n = 102) or not (controls, n = 98). Baseline clinical characteristics were similar between the 2 groups. Despite a trend toward decline, the median high-sensitivity cardiac troponin I (hscTnI) level (P = .256) and the incidence of myocardial infarction (MI) type 4a (P = .106) in the RIPC group 16 hours after PCI procedure was not significantly different from the control group. The RIPC could attenuate the release of a myocardial biomarker but failed to show a significant effect on hscTnI level or MI type 4a incidence after PCI procedure in elderly patients with CHD having DM undergoing elective DES implantation.
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Proliferation of parenchymal microglia is the main source of microgliosis after ischaemic stroke.
Brain
PUBLISHED: 10-22-2013
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Stroke induces rapid activation and expansion of microglia, but the main source of microgliosis is controversial. Here we investigated the formation of microgliosis and infiltration of circulating cells in a photothrombosis stroke model by taking advantage of parabiosis and two-photon microscopy. We found that a small population of blood-derived CX3CR1(GFP/+) cells infiltrated the cerebral parenchyma, but these cells did not proliferate and were phenotypically distinguishable from resident microglia. CX3CR1(GFP/+) infiltrating cells also displayed different kinetics from reactive microglia. The number of CX3CR1(GFP/+) infiltrating cells peaked on Day 5 after stroke and then decreased. The decline of these infiltrating cells was associated with an active apoptotic process. In contrast, reactive microglia were recruited to the ischaemic area continuously during the first week after stroke induction. Immunohistology and in vivo two-photon imaging revealed that cells involved in the process of microgliosis were mainly derived from proliferating resident microglia. Expansion of microglia exhibited a consistent pattern and our in vivo data demonstrated for the first time that microglia underwent active division in regions surrounding the ischaemic core. Together, these results indicated that CX3CR1(GFP/+) infiltrating cells and reactive microglia represented two distinct populations of cells with different functions and therapeutic potentials for the treatment of stroke.
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Cardiac Fibroblasts Recruit Th17 Cells Infiltration Into Myocardium by Secreting CCL20 in CVB3-Induced acute Viral Myocarditis.
Cell. Physiol. Biochem.
PUBLISHED: 10-21-2013
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Aims: Th17 cells contributed to myocardial inflammatory injury in acute viral myocarditis (AVMC), and the migration of these cells were mainly mediated by CCL20-secreting inflammatory cells. However, whether and how the resident cells such as cardiomyocytes and cardiac fibroblasts could mediate Th17 cell migration into the heart remains unclear in AVMC. Methods: The effect of CCL20 on the dynamic alterations of intracardiac Th17 cells and disease severity were investigated through the neutralization of CCL20 in AVMC mice. The key cells releasing CCL20 in the heart and the effects of CCL20-secreting cells on Th17 cell arrest, migration and differentiation were detected in vitro. Results : Neutralization of CCL20 efficiently repressed the myocardial inflammation along with the reduction of Th17 cell infiltrations in the course of AVMC. In vitro, after stimulations of TNF-?, IL-1? and IL-17, cardiac fibroblasts rather than cardiomyocytes could be dominantly induced for CCL20 production. CCL20-secreting cardiac fibroblasts boosted Th17 cell arrest on endothelium, and induce Th17 cell migration. However, CCL20 produced by cardiac fibroblasts had no effect on Th17 cell differentiation and IL-17 production. Conclusions: It firstly suggested that cardiac fibroblasts could recruit Th17 cells infiltration into myocardium by secreting CCL20 in AVMC. © 2013 S. Karger AG, Basel.
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Clinical and pathological features and surgical treatment of Budd-Chiari syndrome-associated hepatocellular carcinoma.
Chin. Med. J.
PUBLISHED: 10-12-2013
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Budd-Chiari syndrome (BCS) is characterized by liver sinusoidal congestion, ischemic liver cell damage, and liver portal hypertension caused by hepatic venous outflow constriction. The aim of this research was to investigate the clinicopathological features of BCS-associated hepatocellular carcinoma (HCC) and explore its surgical treatment and prognosis.
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MEMS Fabry-Perot sensor interrogated by optical system-on-a-chip for simultaneous pressure and temperature sensing.
Opt Express
PUBLISHED: 10-10-2013
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We present a micro-electro-mechanical systems (MEMS) based Fabry-Perot (FP) sensor along with an optical system-on-a-chip (SOC) interrogator for simultaneous pressure and temperature sensing. The sensor employs a simple structure with an air-backed silicon membrane cross-axially bonded to a 45° polished optical fiber. This structure renders two cascaded FP cavities, enabling simultaneous pressure and temperature sensing in close proximity along the optical axis. The optical SOC consists of a broadband source, a MEMS FP tunable filter, a photodetector, and the supporting circuitry, serving as a miniature spectrometer for retrieving the two FP cavity lengths. Within the measured pressure and temperature ranges, experimental results demonstrate that the sensor exhibits a good linear response to external pressure and temperature changes.
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Monolayer graphene/germanium Schottky junction as high-performance self-driven infrared light photodetector.
ACS Appl Mater Interfaces
PUBLISHED: 09-18-2013
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We report on the simple fabrication of monolayer graphene (MLG)/germanium (Ge) heterojunction for infrared (IR) light sensing. It is found that the as-fabricated Schottky junction detector exhibits obvious photovoltaic characteristics, and is sensitive to IR light with high Ilight/Idark ratio of 2 × 10(4) at zero bias voltage. The responsivity and detectivity are as high as 51.8 mA W(-1) and 1.38 × 10(10) cm Hz(1/2) W(-1), respectively. Further photoresponse study reveals that the photovoltaic IR detector displays excellent spectral selectivity with peak sensitivity at 1400 nm, and a fast light response speed of microsecond rise/fall time with good reproducibility and long-term stability. The generality of the above results suggests that the present MLG/Ge IR photodetector would have great potential for future optoelectronic device applications.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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