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Find video protocols related to scientific articles indexed in Pubmed.
A microring resonator photodetector for enhancement in L-band performance.
Opt Express
PUBLISHED: 11-18-2014
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We proposed a microring resonator (MRR) enhanced photodetector (PD) structure. Resonance wavelength enhanced by the MRR amplifies the PD response. At L-band wavelengths, responsivity was doubled for an ultra-short germanium PD of 4 µm employing the MRR structure. Data rates of up to 40 Gb/s were also demonstrated at 1600 nm.
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[Study on the appropriate cutoff points of waist-hip-ratio for Kazakh people over 35 years of age, in Xinjiang].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 11-08-2014
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The aim of this study was to identify the appropriate cutoffs for waist-hip-ratio (WHR) for Kazakh adults at high risk of cardiovascular diseases in Xinjiang.
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Phylogenomics resolves the timing and pattern of insect evolution.
Bernhard Misof, Shanlin Liu, Karen Meusemann, Ralph S Peters, Alexander Donath, Christoph Mayer, Paul B Frandsen, Jessica Ware, Tomáš Flouri, Rolf G Beutel, Oliver Niehuis, Malte Petersen, Fernando Izquierdo-Carrasco, Torsten Wappler, Jes Rust, Andre J Aberer, Ulrike Aspöck, Horst Aspöck, Daniela Bartel, Alexander Blanke, Simon Berger, Alexander Böhm, Thomas R Buckley, Brett Calcott, Junqing Chen, Frank Friedrich, Makiko Fukui, Mari Fujita, Carola Greve, Peter Grobe, Shengchang Gu, Ying Huang, Lars S Jermiin, Akito Y Kawahara, Lars Krogmann, Martin Kubiak, Robert Lanfear, Harald Letsch, Yiyuan Li, Zhenyu Li, Jiguang Li, Haorong Lu, Ryuichiro Machida, Yuta Mashimo, Pashalia Kapli, Duane D McKenna, Guanliang Meng, Yasutaka Nakagaki, José Luis Navarrete-Heredia, Michael Ott, Yanxiang Ou, Günther Pass, Lars Podsiadlowski, Hans Pohl, Björn M von Reumont, Kai Schütte, Kaoru Sekiya, Shota Shimizu, Adam Slipinski, Alexandros Stamatakis, Wenhui Song, Xu Su, Nikolaus U Szucsich, Meihua Tan, Xuemei Tan, Min Tang, Jingbo Tang, Gerald Timelthaler, Shigekazu Tomizuka, Michelle Trautwein, Xiaoli Tong, Toshiki Uchifune, Manfred G Walzl, Brian M Wiegmann, Jeanne Wilbrandt, Benjamin Wipfler, Thomas K F Wong, Qiong Wu, Gengxiong Wu, Yinlong Xie, Shenzhou Yang, Qing Yang, David K Yeates, Kazunori Yoshizawa, Qing Zhang, Rui Zhang, Wenwei Zhang, Yunhui Zhang, Jing Zhao, Chengran Zhou, Lili Zhou, Tanja Ziesmann, Shijie Zou, Yingrui Li, Xun Xu, Yong Zhang, Huanming Yang, Jian Wang, Jun Wang, Karl M Kjer, Xin Zhou.
Science
PUBLISHED: 11-06-2014
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Insects are the most speciose group of animals, but the phylogenetic relationships of many major lineages remain unresolved. We inferred the phylogeny of insects from 1478 protein-coding genes. Phylogenomic analyses of nucleotide and amino acid sequences, with site-specific nucleotide or domain-specific amino acid substitution models, produced statistically robust and congruent results resolving previously controversial phylogenetic relations hips. We dated the origin of insects to the Early Ordovician [~479 million years ago (Ma)], of insect flight to the Early Devonian (~406 Ma), of major extant lineages to the Mississippian (~345 Ma), and the major diversification of holometabolous insects to the Early Cretaceous. Our phylogenomic study provides a comprehensive reliable scaffold for future comparative analyses of evolutionary innovations among insects.
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Oxygen Tension Variation in Ischemic Gastrocnemius Muscle, Marrow, and different Hypoxic Conditions In Vitro.
Med. Sci. Monit.
PUBLISHED: 11-06-2014
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Background Bone marrow stromal cells (BMSCs) play an important role in ischemic limb angiogenesis. BMSCs cultured in vitro can be exposed to oxygen tension much higher than that experienced in vivo. This study assessed oxygen tension in bone marrow and ischemic muscle in vivo, and then identified an appropriate oxygen concentration for culturing BMSCs. Material and Methods Unilateral hind limb ischemia was surgically induced in 30 mice, and tissue oxygen tension in bilateral gastrocnemius muscles and femoral bone marrow was monitored in vivo using a micro-electrode at 24 hours, 1 week, 2 weeks, and 3 weeks after modeling. Media used for culturing normal marrow, muscle, and artery tissue were incubated with various oxygen concentrations, and O2 tension was continuously monitored. Oxygen tension in aortic arterial blood was monitored using a micro-electrode and blood gas analyzer, and the results were compared. Results Oxygen tension in ischemic gastrocnemius muscle reached a nadir at 1 week after ischemic modeling, when histological changes were most noticeable. Culture media incubated with 3%, 6%, and 14% oxygen (the normal oxygen levels of bone marrow, muscle, and arterial blood, respectively) required 9, 6, and 2 hours, respectively, to reach an equilibrated oxygen tension, and oxygen tension was elevated by 1.6-, 1.2-, and 0.4-fold, respectively, upon re-exposure of the media to air. Conclusions Physiological oxygen tension differs in different tissues. A 3% O2 concentration mimics the physiological O2 exposure experienced by BMSCs and represents the hypoxic concentration. Culture medium incubated under hypoxic conditions requires a prolonged period of time to regain equilibrated oxygen tension.
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Prevention of skin carcinogenesis by the ?-blocker carvedilol.
Cancer Prev Res (Phila)
PUBLISHED: 11-05-2014
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The stress-related catecholamine hormones and the ?- and ?-adrenergic receptors (?- and ?-AR) may affect carcinogenesis. The ?-AR GRK/?-arrestin biased agonist carvedilol can induce ?-AR-mediated transactivation of the epidermal growth factor receptor (EGFR). The initial purpose of this study was to determine whether carvedilol, through activation of EGFR, can promote cancer. Carvedilol failed to promote anchorage-independent growth of JB6 P+ cells, a skin cell model used to study tumor promotion. However, at non-toxic concentrations carvedilol dose-dependently inhibited EGF-induced malignant transformation of JB6 P+ cells suggesting that carvedilol has chemopreventive activity against skin cancer. Such effect was not observed for the ?-AR agonist isoproterenol and the ?-AR antagonist atenolol. Gene expression, receptor binding, and functional studies indicate that JB6 P+ cells only express ?2-ARs. Carvedilol, but not atenolol, inhibited EGF-mediated activator protein-1 (AP-1) activation. A topical 7,12-dimethylbenz[?]anthracene (DMBA)-induced skin hyperplasia model in SENCAR mice was utilized to determine the in vivo cancer preventative activity of carvedilol. Both topical and oral carvedilol treatment inhibited DMBA-induced epidermal hyperplasia (P < 0.05) and reduced H-ras mutations; topical treatment being the most potent. However, in models of established cancer, carvedilol had modest to no inhibitory effect on tumor growth of human lung cancer A549 cells in vitro and in vivo. In conclusion, these results suggest that the cardiovascular drug carvedilol may be repurposed for skin cancer chemoprevention, but may not be an effective treatment of established tumors. More broadly, this study suggests that ?-ARs may serve as a novel target for cancer prevention.
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PGF2? regulates the expression of uterine activation proteins via multiple signaling pathways.
Reproduction
PUBLISHED: 10-25-2014
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Prostaglandin F2? (PGF2?) has multiple roles in the birth process in addition to its vital contractile role. Our previous study has demonstrated that PGF2? can modulate uterine activation proteins (UAPs) in cultured pregnant human myometrial smooth muscle cells (HMSMCs). The objective of present study was to define the signaling pathways responsible for PGF2? modulation of UAPs in myometrium. It was found that PGF2? stimulated the expression of connexin43(CX43), prostaglandin endoperoxide synthase2 (PTGS2) and oxytocin receptor (OTR) in cultured HMSMCs. The inhibitors of phospholipase C (PLC) and protein kinase (PK) C blocked PGF2? stimulation of CX43 expression. The inhibitors of ERK, P38 and NF?B also blocked the effect of PGF2? on CX43 expression whereas PI3K and calcineurin/nuclear factor of activated T-cells (NFAT) pathway inhibitors did not reverse the effect of PGF2? on CX43. For PTGS2 and OTR, PLC, PI3K, P38 and calcineurin/NFAT signaling pathways were involved in PGF2? action, whereas PKC and NF?B signaling were not involved. In addition, PGF2? activated NFAT, PI3K, NF?B, ERK and P38 signaling pathways. Our data suggest that PGF2? stimulates CX43, PTGS2 and OTR through divergent signaling pathways.
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[Risk factors of anal function after transabdominal intersphincteric resection for low rectal cancer].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 10-25-2014
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To explore the risk factors of anal function after transabdominal intersphincteric resection(ISR) for low rectal cancer.
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Comparative analysis of the pathogenic mechanisms of street rabies virus strains with different virulence levels.
Biomed. Environ. Sci.
PUBLISHED: 10-25-2014
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To characterize two strains of street rabies virus (RABV) isolated from the brain tissue of cattle from Inner Mongolia. Differences in the histopathological and ultrastructural changes in the brain tissue of infected mice were determined to reveal variation in the pathogenesis of infection between street rabies virus strains.
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Expression of neuronal CXCL10 induced by rabies virus infection initiates infiltration of inflammatory cells, production of chemokines/cytokines and enhancement of Blood-brain Barrier permeability.
J. Virol.
PUBLISHED: 10-24-2014
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It has been shown that enhancement of Blood-brain Barrier (BBB) permeability is modulated by expression of chemokines/cytokines and reduction of tight junction (TJ) proteins in the brains of mice infected with rabies virus (RABV). Since CXCL10 was found to be the most highly expressed chemokine, its temporal and spatial expression was determined in the present study. The expression of the chemokine CXCL10 was initially detected in neurons as early as 3 day post infection (dpi) before it was detected in microglia (6 dpi) and astrocytes (9 dpi) in the brain of RABV-infected mice. Neutralization of CXCL10 by treatment with anti-CXCL10 antibodies reduced IFN-? production and Th17 cell infiltration as well as restored TJ protein expression and BBB permeability. Together, these data suggest that it is the neuronal CXCL-10 that initiates the cascade, leading to the activation of microglia/astrocytes, infiltration of inflammatory cells, expression of chemokines/cytokines, reduction of TJ protein expression, and enhancement of the BBB permeability.
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The -765G>C Polymorphism in the Cyclooxygenase-2 Gene and Digestive System Cancer: a Meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2 (COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer.
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MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4.
Expert Opin. Ther. Targets
PUBLISHED: 10-17-2014
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Although few microRNAs (miRNAs) have been involved in the regulation of post-ischemic cardiac fibrosis, the exact effect and underlying mechanism of miRNAs in cardiac fibrosis remains unclear. Here, we sought to investigate whether microRNA-34 (miR-34) plays a role in the pathogenic development of myocardial fibrosis.
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CMOS compatible monolithic multi-layer Si3N4-on-SOI platform for low-loss high performance silicon photonics dense integration.
Opt Express
PUBLISHED: 10-17-2014
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We demonstrated a low-loss CMOS-compatible multi-layer platform using monolithic back-end-of-line (BEOL) integration. 0.8dB/cm propagation loss is measured for the PECVD Si3N4 waveguide at 1580nm wavelength. The loss is further reduced to 0.24dB/cm at 1270nm wavelength, justifying the platform's feasibility for O-band operation. An inter-layer transition coupler is designed, achieving less than 0.2dB/transition loss across 70nm bandwidth. This is the lowest inter-layer transition loss ever reported. A thermally tuned micro-ring filter is also integrated on the platform, with performance comparable to similar device on SOI platform.
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Efficient silicon nitride grating coupler with distributed Bragg reflectors.
Opt Express
PUBLISHED: 10-17-2014
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In this paper we have designed, fabricated and characterized a high efficiency Silicon nitride grating coupler at 1490 nm. Distributed Bragg reflectors as bottom mirrors are employed to improve the coupling efficiency by reflecting the downward traveling light. The peak coupling efficiency obtained is about -2.5 dB and the 1-dB bandwidth is 53 nm. The fabrication process is CMOS-compatible and is ready to be integrated with photonic circuits.
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Silicon-based traveling-wave photodetector array (Si-TWPDA) with parallel optical feeding.
Opt Express
PUBLISHED: 10-17-2014
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We demonstrate silicon-based traveling-wave photodetector arrays (Si-TWPDAs) with parallel optical feeding by integrating multiple Germanium photodetectors. Such Si-TWPDAs feature the merit of high optical saturation power with remaining the large operation bandwidth. The impedance-matched traveling-wave electrode design takes into account the individual Ge photodetector loading effect. Optical waveguide delay lines are designed in order to balance the electrical phase delay of the traveling-wave electrode. The maximum linear photocurrent at -4V biased voltage are respectively 16 mA, 38 mA, and 65 mA with integrating 1, 2, and 4 photodetectors, upon the saturation power of 40 mW, 100 mW, and 160 mW. This corresponds to a normalized photocurrent generation of >0.32 mA/µm3 and a normalized saturation power of 0.8 mW/µm3. The extracted fiber access responsivity is ~0.42 A/W and the intrinsic responsivity of ~0.82 A/W. The measured 3-dB bandwidth for 4-channel TWPDA is ~20 GHz.
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Upregulated expression of WNT5a increases inflammation and oxidative stress via PI3K/AKT/NF-?B signaling in the granulosa cells of PCOS patients.
J. Clin. Endocrinol. Metab.
PUBLISHED: 10-11-2014
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Context: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied by chronic low-grade inflammation, but the molecular mechanism remains unclear. Objective: We investigated the action of WNT5a in the development of chronic inflammation in PCOS, and the related molecular signaling pathways. Design and Setting: This was a prospective study conducted at the Division of Reproduction Center, Peking University Third Hospital. Patients : A total of 35 PCOS patients and 87 control women who reported to the clinic for the in vitro procedure and the cause of marital infertility was male azoospermia were included. Main Outcome Measures: Mural granulosa cells (GCs) of 35 PCOS patients and 37 controls were collected during oocyte retrieval and gene expression was analyzed. The human KGN cells and mural GCs from 50 control subjects (6-8 samples were pooled together for each experiment) were cultured in vitro. The regulation of inflammation and oxidative stress was confirmed by qPCR, flow-cytometric assay, and dual-luciferase reporter assay after inflammatory stimuli or WNT5a overexpression. Relevant signaling pathways were identified using specific inhibitors. Results: Our data demonstrate significantly elevated WNT5a expression in the mural GCs of PCOS patients compared with the controls. Lipopolysaccharide stimulation increased WNT5a expression in KGN and mural GCs, and BAY-117082 and PDTC (NF-?B inhibitor) treatments suppressed WNT5a mRNA below the control level. WNT5a overexpression also enhanced the expression of inflammation-related genes and increased intracellular reactive oxygen species, whereas both BAY-117082 and LY-294002 (PI3K inhibitor) significantly inhibited WNT5a-induced inflammation and oxidative stress. Conclusions: WNT5a acts as a proinflammatory factor in human ovarian GCs. The upregulated expression of WNT5a in PCOS increases inflammation and oxidative stress predominantly via the PI3K/AKT/NF-?B signaling pathway. The proinflammatory cytokines induced might further enhance WNT5a expression via NF-?B-dependent regulation, indicating a novel regulatory system for chronic inflammation in PCOS.
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A phase I trial of the Fc engineered CD19 antibody XmAb®5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed chronic lymphocytic leukemia.
Blood
PUBLISHED: 10-11-2014
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CD19 is ubiquitously expressed on CLL cells and is therefore an attractive candidate for antibody targeting. XmAb(®)5574 (aka MOR00208) is a novel humanized CD19 monoclonal antibody with an engineered Fc region to enhance Fc gamma receptor binding affinity. Here we report results of a first in human Phase I trial of XmAb5574 in patients with relapsed or refractory CLL. 27 patients were enrolled to 6 escalating dose levels, with expansion at the highest dose level of 12 mg/kg. 9 doses of XmAb5574 were infused over 8 weeks. No maximal tolerated dose was reached, and the drug was generally well tolerated, with infusion reactions of grades 1 and 2 being the most common toxicities. Grade 3 and 4 toxicities occurred in 5 patients and included neutropenia, thrombocytopenia, increased aspartate aminotransferase, febrile neutropenia, and tumor lysis syndrome. XmAb5574 showed preliminary efficacy, with 18 patients (66.7%) responding by physical exam criteria and laboratory studies, and 8 patients (29.6%) responding by CT criteria. Pharmacokinetics showed a half-life of 14 days with clearance that was not dose-dependent. In conclusion, this Phase I trial demonstrates safety and preliminary efficacy of a novel Fc engineered CD19 monoclonal antibody XmAb5574 and justifies movement into the Phase II setting. Trial is registered on clinicaltrials.gov: NCT01161511.
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Endothelial Lipase-384A/C Polymorphism Is Associated with Acute Coronary Syndrome and Lipid Status in Elderly Uygur Patients in Xinjiang.
Genet Test Mol Biomarkers
PUBLISHED: 10-07-2014
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To explore the relationship between the endothelial lipase (EL) gene promoter -384A/C polymorphism and acute coronary syndrome (ACS) and lipid status in elderly Uygur patients in Xinjiang.
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The combination of platelet count and neutrophil lymphocyte ratio is a predictive factor in patients with esophageal squamous cell carcinoma.
Transl Oncol
PUBLISHED: 10-01-2014
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The prognostic value of inflammation indexes in esophageal cancer was not established. In this study, therefore, both prognostic values of Glasgow prognostic score (GPS) and combination of platelet count and neutrophil lymphocyte ratio (COP-NLR) in patients with esophageal squamous cell carcinoma (ESCC) were investigated and compared.
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Heat shock factors in carrot: genome-wide identification, classification, and expression profiles response to abiotic stress.
Mol. Biol. Rep.
PUBLISHED: 09-30-2014
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Heat shock factors (HSFs) play key roles in the response to abiotic stress in eukaryotes. In this study, 35 DcHSFs were identified from carrot (Daucus carota L.) based on the carrot genome database. All 35 DcHSFs were divided into three classes (A, B, and C) according to the structure and phylogenetic relationships of four different plants, namely, Arabidopsis thaliana, Vitis vinifera, Brassica rapa, and Oryza sativa. Comparative analysis of algae, gymnosperms, and angiosperms indicated that the numbers of HSF transcription factors were related to the plant's evolution. The expression profiles of five DcHsf genes (DcHsf 01, DcHsf 02, DcHsf 09, DcHsf 10, and DcHsf 16), which selected from each subfamily (A, B, and C), were detected by quantitative real-time PCR under abiotic stresses (cold, heat, high salinity, and drought) in two carrot cultivars, D. carota L. cvs. Kurodagosun and Junchuanhong. The expression levels of DcHsfs were markedly increased by heat stress, except that of DcHsf 10, which was down regulated. The expression profiles of different DcHsfs in the same class also differed under various stress treatments. The expression profiles of these DcHsfs were also different in tissues of two carrot cultivars. This study is the first to identify and characterize the DcHSF family transcription factors in plants of Apiaceae using whole-genome analysis. The results of this study provide an in-depth understanding of the DcHSF family transcription factors' structure, function, and evolution in carrot.
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Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice.
Appl. Environ. Microbiol.
PUBLISHED: 09-26-2014
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The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis.
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5-HT3a Receptors Modulate Hippocampal Gamma Oscillations by Regulating Synchrony of Parvalbumin-Positive Interneurons.
Cereb. Cortex
PUBLISHED: 09-24-2014
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Gamma-frequency oscillatory activity plays an important role in information integration across brain areas. Disruption in gamma oscillations is implicated in cognitive impairments in psychiatric disorders, and 5-HT3 receptors (5-HT3Rs) are suggested as therapeutic targets for cognitive dysfunction in psychiatric disorders. Using a 5-HT3aR-EGFP transgenic mouse line and inducing gamma oscillations by carbachol in hippocampal slices, we show that activation of 5-HT3aRs, which are exclusively expressed in cholecystokinin (CCK)-containing interneurons, selectively suppressed and desynchronized firings in these interneurons by enhancing spike-frequency accommodation in a small conductance potassium (SK)-channel-dependent manner. Parvalbumin-positive interneurons therefore received diminished inhibitory input leading to increased but desynchronized firings of PV cells. As a consequence, the firing of pyramidal neurons was desynchronized and gamma oscillations were impaired. These effects were independent of 5-HT3aR-mediated CCK release. Our results therefore revealed an important role of 5-HT3aRs in gamma oscillations and identified a novel crosstalk among different types of interneurons for regulation of network oscillations. The functional link between 5-HT3aR and gamma oscillations may have implications for understanding the cognitive impairments in psychiatric disorders.
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Description of Comamonas serinivorans sp. nov., isolated from wheat straw compost.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 09-23-2014
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A Gram-negative bacterium, designated SP-35T, was isolated from compost, and was subjected to a taxonomic study. The isolate was short-rod-shaped, Gram-negative, and no-spore-forming. Phylogenetic analysis based on 16S rRNA sequence comparison indicates that the isolate is related to the genus Comamonas. 16s rRNA sequence analysis showed that its cloest neighbours were the type strains Comamonas odontotermitis Dant 3-8T (96.8%), Comamonas testosteroni DSM 50244T (96.5% similarity), Comamonas guangdongensis CY01T (95.9%) and Comamonas composti YY287T (95.6%). Strain SP-35T was clearly distinguished from all of these strains by using phylogenetic analysis, DNA-DNA hybridization, fatty acid composition data and a range of physiological and biochemical characteristics. The G+C contents of strain SP-35T were 63.1 mol%. The predominant cellular fatty acids were C16:0, C17:0 cyclo, summed feature 3 (C16:1?6c and/or C16:1?7c) and Summed feature 8 (C18:1?6c and/or C18:1?7c). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidlyglycerol. Based on the phenotypic and phylogenetic characteristics, it proposed that strain SP-35T can be classified as Comamonas serinivorans sp. nov., with the type strain SP-35T (=DSM26136T = JCM18194T).
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Favorable Prognosis of Biallelic CEBPA Gene Mutations in Acute Myeloid Leukemia Patients: a meta-analysis.
Eur. J. Haematol.
PUBLISHED: 09-10-2014
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Increasing number of studies suggested that biallelic CEBPA (bi CEBPA) mutations were associated with favorable prognosis in acute myeloid leukemia (AML) patients, but the results remain inconclusive. We therefore present a meta-analysis to evaluate the prognostic value of bi CEBPA mutations in patients with AML.
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Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population.
Nat. Genet.
PUBLISHED: 09-07-2014
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To identify genetic markers for laryngeal squamous cell carcinoma (LSCC), we conducted a genome-wide association study (GWAS) on 993 individuals with LSCC (cases) and 1,995 cancer-free controls from Chinese populations. The most promising variants (association P < 1 × 10(-5)) were then replicated in 3 independent sets including 2,398 cases and 2,804 controls, among which we identified 3 new susceptibility loci at 11q12 (rs174549), 6p21 (rs2857595) and 12q24 (rs10492336). The minor alleles of each of these loci showed protective effects, with odds ratios (95% confidence intervals) of 0.73 (0.68-0.78; P = 1.00 × 10(-20)), 0.78 (0.72-0.84; P = 2.43 × 10(-15)) and 0.71 (0.65-0.77; P = 4.48 × 10(-14)), respectively. None of these variants showed an interaction with smoking or drinking. This is the first GWAS to our knowledge solely on LSCC, and the findings might advance understanding of the etiology of LSCC.
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Liquid-phase growth of platinum nanoparticles on molybdenum trioxide nanosheets: an enhanced catalyst with intrinsic peroxidase-like catalytic activity.
Nanoscale
PUBLISHED: 09-05-2014
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A facile method for the synthesis of metal nanostructure-decorated two-dimensional (2D) semiconductor nanosheets was developed. The solution-processable molybdenum trioxide (MoO3) nanosheet was used as a template for direct liquid-phase growth of platinum nanoparticles (Pt NPs) under ambient conditions. Results show that the Pt NPs with sizes of 1-3 nm were uniformly grown on the MoO3 surface. Importantly, the Pt-MoO3 hybrid nanomaterial exhibits an enhanced peroxidase-like catalytic activity compared to the MoO3 nanosheet, Pt NPs, and their physical mixture under the same conditions. As a proof-of-concept application, the Pt-MoO3 hybrid nanomaterial was used as a high-efficiency peroxidase-mimic for ultrasensitive colorimetric detection of glucose in serum samples. This work provides a promising strategy for design and development of biomimetic catalysts by smart assembly of different dimensional nanomaterials.
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A discrete-time survival model with random effects for designing and analyzing repeated low-dose challenge experiments.
Biostatistics
PUBLISHED: 09-03-2014
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Repeated low-dose (RLD) challenge designs are important in HIV vaccine research. Current methods for RLD designs rely heavily on an assumption of homogeneous risk of infection among animals, which, upon violation, can lead to invalid inferences and underpowered study designs. We propose to fit a discrete-time survival model with random effects that allows for heterogeneity in the risk of infection among animals and allows for predetermined challenge dose changes over time. Based on this model, we derive likelihood ratio tests and estimators for vaccine efficacy. A two-stage approach is proposed for optimizing the RLD design under cost constraints. Simulation studies demonstrate good finite sample properties of the proposed method and its superior performance compared to existing methods. We illustrate the application of the heterogeneous infection risk model on data from a real simian immunodeficiency virus vaccine study using Rhesus Macaques. The results of our study provide useful guidance for future RLD experimental design.
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Characterizing expected benefits of biomarkers in treatment selection.
Biostatistics
PUBLISHED: 09-03-2014
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Biomarkers associated with heterogeneity in subject responses to treatment hold potential for treatment selection. In practice, the decision regarding whether to adopt a treatment-selection marker depends on the effect of using the marker on the rate of targeted disease and on the cost associated with treatment. We propose an expected benefit measure that incorporates both effects to quantify a marker's treatment-selection capacity. This measure builds upon an existing decision-theoretic framework, but is expanded to account for the fact that optimal treatment absent marker information varies with the cost of treatment. In addition, we establish upper and lower bounds on the expected benefit for a perfect treatment-selection rule which provides the basis for a standardized expected benefit measure. We develop model-based estimators for these measures in a randomized trial setting and evaluate their asymptotic properties. An adaptive bootstrap confidence interval is proposed for inference in the presence of non-regularity. Alternative estimators robust to risk model misspecification are also investigated. We illustrate our methods using the Diabetes Control and Complications Trial where we evaluate the expected benefit of baseline hemoglobin A1C in selecting diabetes treatment.
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Regulation of arabidopsis flowering by the histone mark readers MRG1/2 via interaction with CONSTANS to modulate FT expression.
PLoS Genet.
PUBLISHED: 09-01-2014
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Day-length is important for regulating the transition to reproductive development (flowering) in plants. In the model plant Arabidopsis thaliana, the transcription factor CONSTANS (CO) promotes expression of the florigen FLOWERING LOCUS T (FT), constituting a key flowering pathway under long-day photoperiods. Recent studies have revealed that FT expression is regulated by changes of histone modification marks of the FT chromatin, but the epigenetic regulators that directly interact with the CO protein have not been identified. Here, we show that the Arabidopsis Morf Related Gene (MRG) group proteins MRG1 and MRG2 act as H3K4me3/H3K36me3 readers and physically interact with CO to activate FT expression. In vitro binding analyses indicated that the chromodomains of MRG1 and MRG2 preferentially bind H3K4me3/H3K36me3 peptides. The mrg1 mrg2 double mutant exhibits reduced mRNA levels of FT, but not of CO, and shows a late-flowering phenotype under the long-day but not short-day photoperiod growth conditions. MRG2 associates with the chromatin of FT promoter in a way dependent of both CO and H3K4me3/H3K36me3. Vice versa, loss of MRG1 and MRG2 also impairs CO binding at the FT promoter. Crystal structure analyses of MRG2 bound with H3K4me3/H3K36me3 peptides together with mutagenesis analysis in planta further demonstrated that MRG2 function relies on its H3K4me3/H3K36me3-binding activity. Collectively, our results unravel a novel chromatin regulatory mechanism, linking functions of MRG1 and MRG2 proteins, H3K4/H3K36 methylations, and CO in FT activation in the photoperiodic regulation of flowering time in plants.
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Unexpected 1,2-Migration in Metallasilabenzenes: Theoretical Evidence for Reluctance of Silicon to Participate in ? Bonding.
Chem Asian J
PUBLISHED: 08-26-2014
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Density functional theory (DFT) calculations were carried out to investigate the 1,2-migration in metallasilabenzenes. The results suggested that the chloride migration of metallabenzenes is unfavorable due to the loss of aromaticity in the nonaromatic analogues. In sharp contrast, such a migration in metallasilabenzenes is favorable due to the reluctance of silicon to participate in ? bonding. The migration of hydride and methyl group from the metal center to the silicon atom in metallasilabenzenes is computed to be also feasible. In addition, the ? donor ligand and the third row transition metal can stabilize metallasilabenzenes. Thus, such a migration becomes less favorable thermodynamically and kinetically. These findings could be very helpful for synthetic chemists to realize the first metallasilabenzene.
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The construction of hierarchical structure on Ti substrate with superior osteogenic activity and intrinsic antibacterial capability.
Sci Rep
PUBLISHED: 08-22-2014
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The deficient osseointegration and implant-associated infections are pivotal issues for the long-term clinical success of endosteal Ti implants, while development of functional surfaces that can simultaneously overcome these problems remains highly challenging. This study aimed to fabricate sophisticated Ti implant surface with both osteogenic inducing activity and inherent antibacterial ability simply via tailoring surface topographical features. Micro/submciro/nano-scale structure was constructed on Ti by three cumulative subtractive methods, including sequentially conducted sandblasting as well as primary and secondary acid etching treatment. Topographical features of this hierarchical structure can be well tuned by the time of the secondary acid treatment. Ti substrate with mere micro/submicro-scale structure (MS0-Ti) served as a control to examine the influence of hierarchical structures on surface properties and biological activities. Surface analysis indicated that all hierarchically structured surfaces possessed exactly the same surface chemistry as that of MS0-Ti, and all of them showed super-amphiphilicity, high surface free energy, and high protein adsorption capability. Biological evaluations revealed surprisingly antibacterial ability and excellent osteogenic activity for samples with optimized hierarchical structure (MS30-Ti) when compared with MS0-Ti. Consequently, for the first time, a hierarchically structured Ti surface with topography-induced inherent antibacterial capability and excellent osteogenic activity was constructed.
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Met-CCL5 represents an immunotherapy strategy to ameliorate rabies virus infection.
J Neuroinflammation
PUBLISHED: 08-21-2014
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Infection of rabies virus (RABV) causes central nervous system (CNS) dysfunction and results in high mortality in human and animals. However, it is still unclear whether and how CNS inflammation and immune response contribute to RABV infection.
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[Values of a combination of multiple less invasive or non-invasive examinations in the diagnosis of pediatric sputum-negative pulmonary tuberculosis].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 08-21-2014
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To study the values of a combination of multiple less invasive or non-invasive examinations including chest computed tomography (CT) scan, purified protein derivative (PPD) test, erythrocyte sedimentation rate (ESR) test, and C-reactive protein (CRP) test in the diagnosis of pediatric sputum-negative pulmonary tuberculosis (TB).
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Novel myeloid differentiation factor 88, EsMyD88, exhibits EsTube-binding activity in Chinese mitten crab Eriocheir sinensis.
Dev. Comp. Immunol.
PUBLISHED: 08-19-2014
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Myeloid differentiation factor 88 (MyD88) is a universal and essential adapter protein that participates in the activation of the Toll-like receptor/interleukin-1 receptor-mediated signaling pathway. In the present study, a new MyD88 gene (named EsMyD88) was identified in the Chinese mitten crab Eriocheir sinensis. The cDNA of EsMyD88 was 2210?bp long with a 1416?bp open reading frame that encoded a protein with 472 amino acids. Predicted EsMyD88 protein had a death domain at the N-terminal and a TIR domain at the C-terminal. BLASTP and phylogenetic analysis results showed that EsMyD88 was clustered in one group together with other crustaceans MyD88 (SpMyD88, FcMyD88, LvMyD88, and LvMyD88-1). EsMyD88 was detected in all the examined tissues of healthy crabs, and was mainly expressed in the hemocytes and nerves. When normal crabs were challenged with lipopolysaccharide, peptidoglycan, Staphylococcus aureus, Vibrio parahaemolyticus, or Aeromonas hydrophila, the expression levels of EsMyD88 significantly increased either in the hepatopancreas or hemocytes. Results of the pull-down assay showed that EsMyD88 could bind to downstream cytosolic adaptor EsTube. Overexpression of EsMyD88 protein in Drosophila Schneider 2 cells led to the activation of antimicrobial peptide genes. RNA interference assay showed that EsMyD88 is involved in regulating the transcription of ALF1 and ALF2, Cru1 and Cru2, and Lys in crab challenged with V. parahaemolyticus. All the results mentioned earlier indicated that EsMyD88 gene has a key function in antibacterial innate immune defense.
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Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.
Chen Wu, Zhaoming Wang, Xin Song, Xiao-Shan Feng, Christian C Abnet, Jie He, Nan Hu, Xian-Bo Zuo, Wen Tan, Qimin Zhan, Zhibin Hu, Zhonghu He, Weihua Jia, Yifeng Zhou, Kai Yu, Xiao-Ou Shu, Jian-Min Yuan, Wei Zheng, Xue-Ke Zhao, She-Gan Gao, Zhi-Qing Yuan, Fu-You Zhou, Zong-Min Fan, Ji-Li Cui, Hong-Li Lin, Xue-Na Han, Bei Li, Xi Chen, Sanford M Dawsey, Linda Liao, Maxwell P Lee, Ti Ding, You-Lin Qiao, Zhihua Liu, Yu Liu, Dianke Yu, Jiang Chang, Lixuan Wei, Yu-Tang Gao, Woon-Puay Koh, Yong-Bing Xiang, Ze-Zhong Tang, Jin-Hu Fan, Jing-jing Han, Sheng-Li Zhou, Peng Zhang, Dong-Yun Zhang, Yuan Yuan, Ying Huang, Chunling Liu, Kan Zhai, Yan Qiao, Guangfu Jin, Chuanhai Guo, Jianhua Fu, Xiaoping Miao, Changdong Lu, Haijun Yang, Chaoyu Wang, William A Wheeler, Mitchell Gail, Meredith Yeager, Jeff Yuenger, Er-Tao Guo, Ai-li Li, Wei Zhang, Xue-Min Li, Liang-Dan Sun, Bao-Gen Ma, Yan Li, Sa Tang, Xiu-Qing Peng, Jing Liu, Amy Hutchinson, Kevin Jacobs, Carol Giffen, Laurie Burdette, Joseph F Fraumeni, Hongbing Shen, Yang Ke, Yixin Zeng, Tangchun Wu, Peter Kraft, Charles C Chung, Margaret A Tucker, Zhi-Chao Hou, Ya-Li Liu, Yan-Long Hu, Li Wang, Guo Yuan, Li-Sha Chen, Xiao Liu, Teng Ma, Hui Meng, Li Sun, Xin-Min Li, Xiu-Min Li, Jian-Wei Ku, Ying-Fa Zhou, Liu-Qin Yang, Zhou Wang, Yin Li, Qirenwang Qige, Wen-jun Yang, Guang-Yan Lei, Long-qi Chen, En-Min Li, Ling Yuan, Wen-Bin Yue, Ran Wang, Lu-Wen Wang, Xue-Ping Fan, Fang-Heng Zhu, Wei-Xing Zhao, Yi-min Mao, Mei Zhang, Guo-Lan Xing, Ji-Lin Li, Min Han, Jing-Li Ren, Bin Liu, Shu-Wei Ren, Qing-Peng Kong, Feng Li, Ilyar Sheyhidin, Wu Wei, Yan-Rui Zhang, Chang-Wei Feng, Jin Wang, Yu-Hua Yang, Hong-Zhang Hao, Qi-De Bao, Bao-Chi Liu, Ai-Qun Wu, Dong Xie, Wan-Cai Yang, Liang Wang, Xiao-Hang Zhao, Shu-Qing Chen, Jun-Yan Hong, Xue-Jun Zhang, Neal D Freedman, Alisa M Goldstein, Dongxin Lin, Philip R Taylor, Li-dong Wang, Stephen J Chanock.
Nat. Genet.
PUBLISHED: 08-17-2014
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We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
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Identifying optimal biomarker combinations for treatment selection via a robust kernel method.
Biometrics
PUBLISHED: 08-14-2014
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Treatment-selection markers predict an individual's response to different therapies, thus allowing for the selection of a therapy with the best predicted outcome. A good marker-based treatment-selection rule can significantly impact public health through the reduction of the disease burden in a cost-effective manner. Our goal in this article is to use data from randomized trials to identify optimal linear and nonlinear biomarker combinations for treatment selection that minimize the total burden to the population caused by either the targeted disease or its treatment. We frame this objective into a general problem of minimizing a weighted sum of 0-1 loss and propose a novel penalized minimization method that is based on the difference of convex functions algorithm (DCA). The corresponding estimator of marker combinations has a kernel property that allows flexible modeling of linear and nonlinear marker combinations. We compare the proposed methods with existing methods for optimizing treatment regimens such as the logistic regression model and the weighted support vector machine. Performances of different weight functions are also investigated. The application of the proposed method is illustrated using a real example from an HIV vaccine trial: we search for a combination of Fc receptor genes for recommending vaccination in preventing HIV infection.
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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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Patterns and socio-demographic correlates of domain-specific physical activities and their associations with adiposity in the China Kadoorie Biobank study.
BMC Public Health
PUBLISHED: 08-09-2014
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Domain-specific physical activities may have different correlates and health effects, but few large studies have examined these questions, especially their separate associations with adiposity.
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Enhancement of blood-brain barrier permeability is required for intravenously administered virus neutralizing antibodies to clear an established rabies virus infection from the brain and prevent the development of rabies in mice.
Antiviral Res.
PUBLISHED: 08-07-2014
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Rabies virus (RABV) is a neurotropic virus that causes fatal disease in humans and animals. Currently there is no cure for rabies once clinical signs appear. It is believed that once RABV enters the central nervous system (CNS), virus neutralizing antibodies (VNAs) in the periphery cannot pass through the blood-brain barrier (BBB) and into the CNS. Furthermore, it has been hypothesized that VNAs produced in the CNS by invading B cells, rather than those produced in the periphery and then transported into the CNS, are important in clearing RABV from the CNS. In the present study, mouse serum containing VNA was administered intravenously into mice after infection with wild-type RABV. Our studies demonstrate that exogenous administration of VNAs is crucial in the clearance of RABV from the brain and prevent the development of rabies in both immunocompetent and immunocompromised mice as long as the BBB permeability remains enhanced. This present study therefore provides a foundation for the possibility of developing VNA therapy for clinical rabies in humans.
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Cardiovascular risks in Kazakh population in Xinjiang Province of China.
Ethn Dis
PUBLISHED: 07-29-2014
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Assess the cardiovascular risks in Kazakh population in Ili of Xinjiang Province.
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A mouse line for inducible and reversible silencing of specific neurons.
Mol Brain
PUBLISHED: 07-24-2014
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BackgroundGenetic methods for inducibly and reversibly inhibiting neuronal activity of specific neurons are critical for exploring the functions of neuronal circuits. The engineered human glycine receptor, called ivermectin (IVM)-gated silencing receptor (IVMR), has been shown to possess this ability in vitro.ResultsHere we generated a mouse line, in which the IVMR coding sequence was inserted into the ROSA26 locus downstream of a loxP-flanked STOP cassette. Specific Cre-mediated IVMR expression was revealed by mis-expression of Cre in the striatum and by crossing with several Cre lines. Behavioral alteration was observed in Rosa26-IVMR mice with unilateral striatal Cre expression after systemic administration of IVM, and it could be re-initiated when IVM was applied again. A dramatic reduction in neuron firing was recorded in IVM-treated free moving Rosa26-IVMR;Emx1-Cre mice, and neuronal excitability was reduced within minutes as shown by recording in brain slice.ConclusionThis Rosa26-IVMR mouse line provides a powerful tool for exploring selective circuit functions in freely behaving mice.
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Acidophilic denitrifiers dominate the N2O production in a 100-year-old tea orchard soil.
Environ Sci Pollut Res Int
PUBLISHED: 07-21-2014
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Aerobic denitrification is the main process for high N2O production in acid tea field soil. However, the biological mechanisms for the high emission are not fully understood. In this study, we examined N2O emission and denitrifier communities in 100-year-old tea soils with four pH levels (3.71, 5.11, 6.19, and 7.41) and four nitrate concentration (0, 50, 200, and 1000 mg kg(-1) of NO3 (-)-N) addition. Results showed the highest N2O emission (10.1 mg kg(-1) over 21 days) from the soil at pH 3.71 with 1000 mg kg(-1) NO3 (-) addition. The N2O reduction and denitrification enzyme activity in the acid soils (pH <7.0) were significantly higher than that of soils at pH 7.41. Moreover, TRF 78 of nirS and TRF 187 of nosZ dominated in soils of pH 3.71, suggesting an important role of acidophilic denitrifiers in N2O production and reduction. CCA analysis also showed a negative correlation between the dominant denitrifier ecotypes (nirS TRF 78, nosZ TRF 187) and soil pH. The representative sequences were identical to those of cultivated denitrifiers from acidic soils via phylogenetic tree analysis. Our results showed that the acidophilic denitrifier adaptation to the acid environment results in high N2O emission in this highly acidic tea soil.
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Transcript profiling of structural genes involved in cyanidin-based anthocyanin biosynthesis between purple and non-purple carrot (Daucus carota L.) cultivars reveals distinct patterns.
BMC Plant Biol.
PUBLISHED: 07-03-2014
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Carrots (Daucus carota L.) are among the 10 most economically important vegetable crops grown worldwide. Purple carrot cultivars accumulate rich cyanidin-based anthocyanins in a light-independent manner in their taproots whereas other carrot color types do not. Anthocyanins are important secondary metabolites in plants, protecting them from damage caused by strong light, heavy metals, and pathogens. Furthermore, they are important nutrients for human health. Molecular mechanisms underlying anthocyanin accumulation in purple carrot cultivars and loss of anthocyanin production in non-purple carrot cultivars remain unknown.
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Laparoscopic Transabdominal Approach Partial Intersphincteric Resection for Low Rectal Cancer: Surgical Feasibility and Intermediate-Term Outcome.
Ann. Surg. Oncol.
PUBLISHED: 07-03-2014
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Traditionally, conventional intersphincteric resection requires a combined abdominal and perineal approach and a handsewn coloanal anastomosis procedure, which is difficult to accomplish via the perineal approach. A completely abdominal approach partial intersphincteric resection (APISR) with laparoscopy can simplify the anastomosis procedure. This study evaluated the intermediate-term oncological and functional results of laparoscopic versus open APISR for low rectal cancer.
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Optimization of technological parameters for preparation of lycopene microcapsules.
J Food Sci Technol
PUBLISHED: 06-27-2014
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Lycopene belongs to the carotenoid family with high degree of unsaturation and all-trans form. Lycopene is easy to isomerize and auto oxide by heat, light, oxygen and different food matrices. With an increasing understanding of the health benefit of lycopene, to enhance stability and bioavailability of lycopene, ultrasonic emulsification was used to prepare lycopene microcapsules in this article. The results optimized by response surface methodology (RSM) for microcapsules consisted of four major steps: (1) 0.54 g glycerin monostearate was fully dissolved in 5 mL ethyl acetate and then added 0.02 g lycopene to form an organic phase, 100.7 mL distilled water which dissolved 0.61 g synperonic pe(R)/F68 as the aqueous phase; (2) the organic phase was pulled into the aqueous phase under stirring at 60 °C water bath for 5 min; (3) the mixture was then ultrasonic homogenized at 380 W for 20 min to form a homogenous emulsion; (4) the resulting emulsion was rotary evaporated at 50 °C water bath for 10 min under a pressure of 20 MPa. Encapsulation efficiency (EE) of lycopene microcapsules under the optimized conditions approached to 64.4%.
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Solid-state characterization and transformation of various creatine phosphate sodium hydrates.
J Pharm Sci
PUBLISHED: 06-18-2014
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Creatine phosphate sodium (CPS) salt is a first-line cardiovascular drug for severe diastolic heart failure. The drug exists in different hydrate forms. The marketed drug form was determined as CPS·4.5H2 O (H1); however, the reference standard was supplied as CPS·6H2 O (H2). In this work, we present two newly identified hydrate forms: a thermodynamically stable low hydrate form, CPS·1.5H2 O (H3), and a pressure-sensitive transit form, CPS·7H2 O (H4). The hydrate forms were discovered through a comprehensive solid-state screening experiment and fully characterized using a range of analytical techniques including X-ray powder diffraction (XRPD), FTIR, Raman spectroscopy, hot-stage microscopy (HSM), thermogravimetric analysis, and differential scanning calorimetry. Stability tests revealed that H3 was the most stable hydrate under thermal stimulation. H4 is a pressure-sensitive hydrate and easily transforms to H2 and then H1 upon grinding. The form transformation process was closely monitored using the HSM, variable-temperature XRPD (VT-XRPD), and VT-Raman spectroscopy techniques. Specifically, the transformation of H4 to H1 is characterized in a single-crystal-to-single-crystal transformation process. The newly discovered hydrate form H3 has superior physicochemical properties than the marketed forms and is worthy of further development. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3688-3695, 2014.
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Changes in coagulation and fibrinolytic indices in women with polycystic ovarian syndrome undergoing controlled ovarian hyperstimulation.
Int J Endocrinol
PUBLISHED: 05-26-2014
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Background. Polycystic ovarian syndrome (PCOS) women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment always attain a low cumulative pregnancy rate disaccording with the satisfactory number of oocytes. Objective. We aim to evaluate the status of coagulation and fibrinolytic system in PCOS patients undergoing controlled ovarian hyperstimulation (COH) process. Method. Of the 97 women, 30 patients with PCOS composed the study group; 67 women of child-bearing age with normal endocrine function composed the control group. All participants underwent GnRH agonist standard long protocol, and plasma HCY, FVIII, FX, and D-dimer levels as well as hormone parameters were measured at day of full downregulation, hCG priming, and embryos transfer. Results. On day of full downregulation, FX levels were significantly higher in PCOS group (P < 0.01). On hCG priming day, FX and estrogen levels in PCOS group were higher than in the control group and FVIII levels were significantly lower on day of embryos transfer whereas FX and E2 levels were significantly higher in PCOS group. Conclusion. Hypercoagulable state during peri-implantation phase would probably lead to poor microcirculation of endometrium and be one of the most important disadvantages of successful implantation and subsequent clinical pregnancy.
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Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor.
Cancer Cell
PUBLISHED: 05-09-2014
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Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor suppressor protein, which is an ubiquitin ligase component, leading to their destruction. In the case of ETS1, however, phosphorylation of a neighboring tyrosine residue by Src family kinases disrupts COP1 binding, thereby stabilizing ETS1. Src-dependent accumulation of ETS1 in breast cancer cells promotes anchorage-independent growth in vitro and tumor growth in vivo. These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases.
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Genome-wide analysis of DNA methylation in UVB- and DMBA/TPA-induced mouse skin cancer models.
Life Sci.
PUBLISHED: 05-06-2014
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Ultraviolet irradiation and carcinogens have been reported to induce epigenetic alterations, which potentially contribute to the development of skin cancer. We aimed to study the genome-wide DNA methylation profiles of skin cancers induced by ultraviolet B (UVB) irradiation and 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-1,3-acetate (TPA).
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Hypofractionated radiotherapy induces miR-34a expression and enhances apoptosis in human nasopharyngeal carcinoma cells.
Int. J. Mol. Med.
PUBLISHED: 04-26-2014
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Nasopharyngeal carcinoma (NPC) is a relatively radiosensitive disease. However, the therapeutic effects of radiotherapy are not always satisfactory due to radioresistance. The hypofractionated schema is currently widely used in clinical practice. In the present study, we investigated the effects of hypofractionated radiotherapy on NPC cells and explored the mechanisms involved. In addition, we aimed to determine the role of miR-34a in the effects of hypofractionated radiotherapy and whether these effects occur in a p53-dependent manner. For this purpose, we used CNE1 and CNE2 NPC cells which were subjected to hyperfractionated and hypofractionated radiotherapy. The viability of the cells was measured by MTT assay and acridine orange (AO) and ethidium bromide (EB) staining was used to observe morphological changes. In addition, Annexin V-propidium iodide (PI) staining and flow cytometry were used to determine the number of apoptotic cells and mRNA and protein expression was measured by qPCR and western blot analysis, respectively. The results revealed that hypofractionated radiotherapy enhanced apoptosis and increased the expression of miR-34a and p53 in the NPC cells. In addition, it stimulated p53 promoter activity and downregulated the protein expression of c-Myc in the human NPC cells. Furthermore, the knockdown of miR-34a suppressed the growth inhibitory effects induced by hypofractionated radiotherapy. Thus, our results suggest that the enhanced apoptosis of NPC cells may be associated with the miR-34a-mediated suppression of c-Myc in a p53-dependent manner.
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Cellular FLICE-like inhibitory protein protects against cardiac hypertrophy by blocking ASK1/p38 signaling in mice.
Mol. Cell. Biochem.
PUBLISHED: 04-15-2014
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Cellular FLICE-like inhibitory protein (Flip) is a negative regulator of nuclear factor ?B signaling which has been shown previously to complicate with cardiac hypertrophy. In the present study, we tested the hypothesis that the knockout of Flip would increase cardiac hypertrophy in vivo and in vitro. The effects of Flip knockout on cardiac hypertrophy were investigated using in vitro and in vivo models. Flip was downregulated in transverse aortic constriction (TAC)-induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 1 h. An in vivo, heart hypertrophy model, was performed by TAC in Flip knockdown and sham mice. The extent of hypertrophy of heart was quantitated by echocardiography, and further confirmed by pathological and molecular examination of heart tissue samples. Conditional knockout of Flip in the murine heart increases the hypertrophic response induced by TAC, whereas cardiac function was preserved with reduced Flip levels in response to hypertrophic stimuli. Western blot experiments further showed Flip knockout activated markedly ASK1/P38 signaling cascades in vivo and in vitro. In conclusion, Flip preserves cardiac functions and inhibits cardiac hypertrophy partially by blocking ASK1/P38 signaling.
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Post-trauma growth in a mainland Chinese population with chronic skin disease.
Int. J. Dermatol.
PUBLISHED: 03-22-2014
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This study aimed to determine the underlying factor structure of the mainland Chinese version of the Post-traumatic Growth Inventory (PTGI-MC) and the determinants of post-trauma growth (PTG).
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Fast transmission from the dopaminergic ventral midbrain to the sensory cortex of awake primates.
Brain Struct Funct
PUBLISHED: 03-20-2014
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Motivated by the increasing evidence that auditory cortex is under control of dopaminergic cell structures of the ventral midbrain, we studied how the ventral tegmental area and substantia nigra affect neuronal activity in auditory cortex. We electrically stimulated 567 deep brain sites in total within and in the vicinity of the two dopaminergic ventral midbrain structures and at the same time, recorded local field potentials and neuronal discharges in cortex. In experiments conducted on three awake macaque monkeys, we found that electrical stimulation of the dopaminergic ventral midbrain resulted in short-latency (~35 ms) phasic activations in all cortical layers of auditory cortex. We were also able to demonstrate similar activations in secondary somatosensory cortex and superior temporal polysensory cortex. The electrically evoked responses in these parts of sensory cortex were similar to those previously described for prefrontal cortex. Moreover, these phasic responses could be reversibly altered by the dopamine D1-receptor antagonist SCH23390 for several tens of minutes. Thus, we speculate that the dopaminergic ventral midbrain exerts a temporally precise, phasic influence on sensory cortex using fast-acting non-dopaminergic transmitters and that their effects are modulated by dopamine on a longer timescale. Our findings suggest that some of the information carried by the neuronal discharges in the dopaminergic ventral midbrain, such as the motivational value or the motivational salience, is transmitted to auditory cortex and other parts of sensory cortex. The mesocortical pathway may thus contribute to the representation of non-auditory events in the auditory cortex and to its associative functions.
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Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth.
J. Clin. Invest.
PUBLISHED: 02-19-2014
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Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and estrogen-related receptor ? (ERBB2) amplification. Here, we found that inducible I?B kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK alone does not. CYT387 treatment inhibited activation of both NF-?B and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds.
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Effect of total dose and fraction size on survival of patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: A phase 2, single-center, randomized controlled trial.
Cancer
PUBLISHED: 01-24-2014
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The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model.
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Positional Isomerization of A Non-Cleavable Combi-Molecule Dramatically Altered Tumor Cell Response Profile.
Chem Biol Drug Des
PUBLISHED: 01-16-2014
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To potentiate the quinazoline-based inhibitor of the epidermal growth factor receptor (EGFR), a chloroethyl alkylating moiety was appended to its 6-position. This led to molecules with extremely strong EGFR inhibitory potency and anomalously strong DNA-damaging potential. To assess the role of the chloroethyl group on potency, we designed a molecule in which it is shifted to the 7-position where it would be less reactive and away from the cys773 of the EGFR ATP site. The results showed that (i) ZR2009 was 10-fold less potent than its positional isomer ZR2003 in EGFR tyrosine kinase inhibition, (ii) it consistently exhibited significantly weaker antiproliferative potency than ZR2003, (iii) in reversibility assays, while ZR2003 induced sustained inhibition of EGFR phosphorylation, ZR2009 inhibitory activity was partially reversed, and (iv) likewise, ZR2009 significantly lost its activity in short exposure growth inhibitory assays and induced lower levels of DNA damage than ZR2003. Molecular modeling suggested that while the chloroethylamino group in ZR2003 was at 3.5 Å away from Cys773, that of ZR2009 was at 6.3 Å. The results in toto suggest that, while the chloroethyl is a strong alkylating group, its appendage to the 6-position is optimal for DNA damage, sustained EGFR, and growth inhibition.
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Epithelial sodium channel inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives.
J Clin Hypertens (Greenwich)
PUBLISHED: 01-14-2014
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Overactivity of the epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In an open-labeled, nonplacebo-controlled clinical trial (Clinicaltrials.gov: NCT-01308983), the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17). The mean body mass index of participants was 28.45±1.30 kg/m(2) . Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid-radial pulse wave velocity were significantly reduced by -7.06±2.25 mm Hg, -7.68±2.56 mm Hg, and -0.72±0.33 m/s, respectively, whereas flow-mediated dilation was significantly increased by 2.2±0.9%. Following amiloride monotherapy for 4 weeks, a significant increase in serum aldosterone was observed (5.85±2.45 ng/dL). ENaC inhibition by amiloride may be used as an early intervention to halt the progression to full hypertension and cardiovascular disease in young adults with prehypertension.
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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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Clinical features of airway malacia in children: a retrospective analysis of 459 patients.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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To investigate the clinical features of airway malacia in children.
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A new inflammation index is useful for patients with esophageal squamous cell carcinoma.
Onco Targets Ther
PUBLISHED: 01-01-2014
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The prognostic value of inflammation indexes in esophageal cancer has not been established. Recent studies have shown that the advanced lung cancer inflammation index (ALI) is a useful predictive factor. The purpose of the current study was to determine whether the ALI is useful for predicting long-term survival in patients with esophageal squamous cell carcinoma (ESCC).
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Abnormal anxiety- and depression-like behaviors in mice lacking both central serotonergic neurons and pancreatic islet cells.
Front Behav Neurosci
PUBLISHED: 01-01-2014
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Dysfunction of central serotonin (5-HT) system has been proposed to be one of the underlying mechanisms for anxiety and depression, and the association of diabetes mellitus and psychiatric disorders has been noticed by the high prevalence of anxiety/depression in patients with diabetes mellitus. This promoted us to examine these behaviors in central 5-HT-deficient mice and those also suffering with diabetes mellitus. Mice lacking either 5-HT or central serotonergic neurons were generated by conditional deletion of Tph2 or Lmx1b respectively. Simultaneous depletion of both central serotonergic neurons and pancreatic islet cells was achieved by administration of diphtheria toxin (DT) in Pet1-Cre;Rosa26-DT receptor (DTR) mice. The central 5-HT-deficient mice showed reduced anxiety-like behaviors as they spent more time in and entered more often into the light box in the light/dark box test compared with controls; similar results were observed in the elevated plus maze test. However, they displayed no differences in the immobility time of the forced swimming and tail suspension tests suggesting normal depression-like behaviors in central 5-HT-deficient mice. As expected, DT-treated Pet1-Cre;Rosa26-DTR mice lacking both central serotonergic neurons and pancreatic islet endocrine cells exhibited several classic diabetic symptoms. Interestingly, they displayed increased anxiety-like behaviors but reduced immobility time in the forced swimming and tail suspension tests. Furthermore, the hippocampal neurogenesis was dramatically enhanced in these mice. These results suggest that the deficiency of central 5-HT may not be sufficient to induce anxiety/depression-like behaviors in mice, and the enhanced hippocampal neurogenesis may contribute to the altered depression-like behaviors in the 5-HT-deficient mice with diabetes. Our current investigation provides understanding the relationship between diabetes mellitus and psychiatric disorders.
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Retrospective analysis of 234 nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis: therapeutic approaches and prognostic factors.
PLoS ONE
PUBLISHED: 01-01-2014
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The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis.
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Is there an association between ABO blood group and overall survival in patients with esophageal squamous cell carcinoma?
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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The relationship between ABO blood group and clinical characteristics had been studied in several cancers. However, its role in esophageal cancer (EC) is unclear. The aim of this study was to determine whether ABO blood group is associated with overall survival in patients with esophageal squamous cell carcinoma (ESCC).
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A scoring system to predict inferior mesenteric artery lymph node metastasis and prognostic value of its involvement in rectal cancer.
Int J Colorectal Dis
PUBLISHED: 12-04-2013
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The aim of this study is to establish a prediction scoring system for inferior mesenteric artery (IMA) lymph node metastasis and to assess the prognostic impact of dissection of positive IMA node on patients with stage III rectal cancer.
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Knowledge, attitude and practice of antibiotics: a questionnaire study among 2500 Chinese students.
BMC Med Educ
PUBLISHED: 12-03-2013
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Recently, many scientists including bacteriologists have begun to focus on social aspects of antibiotic management especially the knowledge, attitude and practice (KAP) among the general population regarding antibiotic use. However, relatively few works have published on the relationship between KAP and medical education. In this study, we analyze the present status of Chinese medical (MS)- and non-medical (NS) students KAP on the use of antibiotics, and examine the influence of Chinese medical curriculum on the appropriate usage of antibiotics among medical students.
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Branched-chain amino acid requirements for enterally fed term neonates in the first month of life.
Am. J. Clin. Nutr.
PUBLISHED: 11-27-2013
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Knowledge of essential amino acid requirements in infants is important because excessive intake of protein can lead to increased long-term morbidity such as obesity. A deficient intake may lead to suboptimal growth and impaired neurodevelopment. The current recommended branched-chain amino acid requirements in infants aged 0-1 mo are based on the amino acid content of human milk.
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IL-35: a potential target for the treatment of atherosclerosis.
Pharmazie
PUBLISHED: 11-27-2013
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The imbalance of anti- inflammatory/pro-inflammatory cytokines plays an important role in the process of atherosclerosis. IL-35 is an anti-inflammatory cytokine comprising the p35 subunit of IL-12 and the subunit Epstein-Barr virus (EBV) -induced gene 3(EBI3). Accumulating evidence showed that IL-35 up-regulates the expression of anti-inflammatory cytokines, induces the generation of CD4 + regulatory T cells, inhibits CD4 + effector T cells response and other target cells activity, and reduces the progression of inflammatory and autoimmune diseases. In addition, it has been found that Ebi3 and p35 strongly coexpressed in human advanced lesions. Therefore, we hypothesize that IL-35 may become a novel target for the treatment of atherosclerosis. Further studies are required to investigate the precise effect and the signaling pathway of IL-35 in atherosclerosis process.
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Measurement Error Corrected Sodium and Potassium Intake Estimation Using 24-Hour Urinary Excretion.
Hypertension
PUBLISHED: 11-25-2013
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Epidemiological studies of the association of sodium and potassium intake with cardiovascular disease risk have almost exclusively relied on self-reported dietary data. Here, 24-hour urinary excretion assessments are used to correct the dietary self-report data for measurement error under the assumption that 24-hour urine recovery provides a biomarker that differs from usual intake according to a classical measurement model. Under this assumption, dietary self-reports underestimate sodium by 0% to 15%, overestimate potassium by 8% to 15%, and underestimate sodium/potassium ratio by ?20% using food frequency questionnaires, 4-day food records, or three 24-hour dietary recalls in Womens Health Initiative studies. Calibration equations are developed by linear regression of log-transformed 24-hour urine assessments on corresponding log-transformed self-report assessments and several study subject characteristics. For each self-report method, the calibration equations turned out to depend on race and age and strongly on body mass index. After adjustment for temporal variation, calibration equations using food records or recalls explained 45% to 50% of the variation in (log-transformed) 24-hour urine assessments for sodium, 60% to 70% of the variation for potassium, and 55% to 60% of the variation for sodium/potassium ratio. These equations may be suitable for use in epidemiological disease association studies among postmenopausal women. The corresponding signals from food frequency questionnaire data were weak, but calibration equations for the ratios of sodium and potassium/total energy explained ?35%, 50%, and 45% of log-biomarker variation for sodium, potassium, and their ratio, respectively, after the adjustment for temporal biomarker variation and may be suitable for cautious use in epidemiological studies.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
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Sensory input is required for callosal axon targeting in the somatosensory cortex.
Mol Brain
PUBLISHED: 11-24-2013
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Sensory input is generally thought to be necessary for refining and consolidating neuronal connections during brain development. We here report that cortical callosal axons in somatosensory cortex require sensory input for their target selection in contralateral cortex.
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Excellent Electromagnetic Absorption Properties of Poly(3,4-ethylenedioxythiophene)-Reduced Graphene Oxide-Co3O4 Composites Prepared by a Hydrothermal Method.
ACS Appl Mater Interfaces
PUBLISHED: 11-20-2013
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The ternary composites of poly(3,4-ethylenedioxythiophene)-reduced graphene oxide-Co3O4 (PEDOT-RGO-Co3O4) were synthesized and the electromagnetic absorption property of the composites was investigated. The structure of the composites was characterized with Fourier-transform infrared spectra, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscope. The electromagnetic parameters indicate the enhanced electromagnetic absorption property of the composites was attributed to the better impedance matching. On the basis of the above characterization, an electromagnetic complementary theory was proposed to explain the impedance matching. It can be found that the maximum reflection loss of PEDOT-RGO-Co3O4 can reach -51.1 dB at 10.7 GHz, and the bandwidth exceeding -10 dB is 3.1 GHz with absorber thickness of 2.0 mm. Therefore, the PEDOT-RGO-Co3O4 composites, with such excellent electromagnetic absorption properties and wide absorption bandwidth, can be used as a new kind of candidate for microwave absorbing materials.
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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.