JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
[Relationship between hepatocellular carcinoma and the interaction between hMSH2 polymorphisms and environmental factors].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 11-05-2014
Show Abstract
Hide Abstract
To use a hospital-based case-control study design to investigate the relationship between hepatocellular carcinoma (HCC) and the interaction of polymorphisms in the human mismatch repair gene,hMSH2,with environmental factors.
Related JoVE Video
All-optical non-conjugated wavelength multicasting of QPSK signal with capability of phase regeneration.
Opt Express
PUBLISHED: 10-17-2014
Show Abstract
Hide Abstract
We propose all-optical one-to-three non-conjugated wavelength multicasting of QPSK signal with capability of phase regeneration, using dual-conjugated-pump phase sensitive amplification (PSA). Based on the seven-wave model, we can obtain phase transfer functions of individual multicasting channel. Different from two multicasting copies, the phase regeneration performance of input signal is determined by the nonlinear phase shift. Moreover, the optimal squeezing points of three multicasting channels have a deviation. Thus, there exists a regeneration performance trade-off among three multicasting channels. Our numerical simulation shows that the error vector magnitude (EVM) of 50 Gb/s QPSK signal can be successfully improved when both nonlinear phase shift and four-state position in its constellation are optimized. The calculated BER curves verify that the OSNR penalties of three multicasting channels are improved by around 1dB at BER = 10-3.
Related JoVE Video
In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes.
Nanoscale
PUBLISHED: 10-17-2014
Show Abstract
Hide Abstract
As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.
Related JoVE Video
Extrarenal Phenotypes of the UT-B Knockout Mouse.
Subcell. Biochem.
PUBLISHED: 10-10-2014
Show Abstract
Hide Abstract
The urea transporter UT-B is expressed in multiple tissues including erythrocytes, kidney, brain, heart, liver, colon, bone marrow, spleen, lung, skeletal muscle, bladder, prostate, and testis in mammals. Phenotype analysis of UT-B-null mice has confirmed that UT-B deletion results in a urea-selective urine-concentrating defect (see Chap. 9 ). The functional significance of UT-B in extrarenal tissues studied in the UT-B-null mouse is discussed in this chapter. UT-B-null mice present depression-like behavior with urea accumulation and nitric oxide reduction in the hippocampus. UT-B deletion causes a cardiac conduction defect, and TNNT2 and ANP expression changes in the aged UT-B-null heart. UT-B also plays a very important role in protecting bladder urothelium from DNA damage and apoptosis by regulating the urea concentration in urothelial cells. UT-B functional deficiency results in urea accumulation in the testis and early maturation of the male reproductive system. These results show that UT-B is an indispensable transporter involved in maintaining physiological functions in different tissues.
Related JoVE Video
[A review of atmospheric aerosol research by using polarization remote sensing].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 10-02-2014
Show Abstract
Hide Abstract
In the present paper, aerosol research by using polarization remote sensing in last two decades (1993-2013) was reviewed, including aerosol researches based on POLDER/PARASOL, APS(Aerosol Polarimetry Sensor), Polarized Airborne camera and Ground-based measurements. We emphasize the following three aspects: (1) The retrieval algorithms developed for land and marine aerosol by using POLDER/PARASOL; The validation and application of POLDER/PARASOL AOD, and cross-comparison with AOD of other satellites, such as MODIS AOD. (2) The retrieval algorithms developed for land and marine aerosol by using MICROPOL and RSP/APS. We also introduce the new progress in aerosol research based on The Directional Polarimetric Camera (DPC), which was produced by Anhui Institute of Optics and Fine Mechanics, Chinese Academy of Sciences (CAS). (3) The aerosol retrieval algorithms by using measurements from ground-based instruments, such as CE318-2 and CE318-DP. The retrieval results from spaceborne sensors, airborne camera and ground-based measurements include total AOD, fine-mode AOD, coarse-mode AOD, size distribution, particle shape, complex refractive indices, single scattering albedo, scattering phase function, polarization phase function and AOD above cloud. Finally, based on the research, the authors present the problems and prospects of atmospheric aerosol research by using polarization remote sensing, and provide a valuable reference for the future studies of atmospheric aerosol.
Related JoVE Video
Increasing gene discovery and coverage using RNA-seq of globin RNA reduced porcine blood samples.
BMC Genomics
PUBLISHED: 10-01-2014
Show Abstract
Hide Abstract
Transcriptome analysis of porcine whole blood has several applications, which include deciphering genetic mechanisms for host responses to viral infection and vaccination. The abundance of alpha- and beta-globin transcripts in blood, however, impedes the ability to cost-effectively detect transcripts of low abundance. Although protocols exist for reduction of globin transcripts from human and mouse/rat blood, preliminary work demonstrated these are not useful for porcine blood Globin Reduction (GR). Our objectives were to develop a porcine specific GR protocol and to evaluate the GR effects on gene discovery and sequence read coverage in RNA-sequencing (RNA-seq) experiments.
Related JoVE Video
Defect-induced strong localization of uranium dicarbide on the graphene surface.
Phys Chem Chem Phys
PUBLISHED: 09-20-2014
Show Abstract
Hide Abstract
Defects such as the most stable hexavacancy (V6) distribute widely on neutron-irradiated graphite surfaces, which play a dominant role in immobilizing radioactive products released from nuclear fuels. By performing DFT calculations, we explore the interaction of gaseous uranium dicarbide (UC2) molecules on a graphene nanosheet with a V6 defect, in order to investigate the behavior of the representative vapor species of uranium carbide fuels in reactor cores. Results suggest that UC2 can be trapped in the V6 defect with considerable binding energy of >10 eV, with all the six dangling bonds of the V6 defect being saturated by UC2. Bonding nature analyses also reveal that the U-C interaction lies in the synergistic interplay between electrostatic and covalent interaction with extensive participation of U valence electrons from 5f to 7p orbitals, which further stimulate polarization of semi-core 6p orbitals and their subsequent contributions to the bonding. This strong interaction leads to a favorable binding of UC2 to the defective graphite surface, which reduces the capability of nuclear graphite to retain harmful fission products by the vacancies being filled with UC2. These findings highlight substantial chemical reactivity and strong localization of UC2 on the widespread V6 defects in nuclear graphite, and may provide an important reference in establishing modern nuclear reactor safety at the atomic level.
Related JoVE Video
[A family with two children diagnosed with aspartylglucosaminuria-case report and literature review].
Zhonghua Er Ke Za Zhi
PUBLISHED: 09-06-2014
Show Abstract
Hide Abstract
The authors sought to investigate the clinical features and characteristics of genetic mutation in patients with aspartylglucosaminuria.
Related JoVE Video
Berberine induces hERG channel deficiency through trafficking inhibition.
Cell. Physiol. Biochem.
PUBLISHED: 08-18-2014
Show Abstract
Hide Abstract
The human ether-a-go-go-related gene (hERG) encodes the ? subunit of the IKr, which plays an essential role in repolarization of action potentials. hERG channels are targeted by various pro-arrhythmic drugs. Berberine (BBR) was previously found to acutely inhibit hERG currents and prolong action potential duration. The present study aimed to determine long-term effects of BBR on the expression of 135kDa/155kDa hERG and the mechanism.
Related JoVE Video
A new tumour suppression mechanism by p27Kip1: EGFR down-regulation mediated by JNK/c-Jun pathway inhibition.
Biochem. J.
PUBLISHED: 08-15-2014
Show Abstract
Hide Abstract
p27Kip1 is a potent inhibitor of cyclin-dependent kinases that drive G1-to-S cell-cycle transition. Reduced p27Kip1 expression is prevalent in a wide range of human tumours; however, the exact mechanism(s) of p27Kip1-mediated tumour suppression remains obscure. In the present study, we identified a close inverse relationship between p27Kip1 and EGFR (epidermal growth factor receptor) expression: the parental T24 human bladder cancer cells had high p27Kip1 expression but low EGFR expression and, in striking contrast, the metastatic derivative of T24 (T24T) had low p27Kip1 expression but high EGFR expression. This relationship was also found in various human cancer tissues, and was not only just correlative but also causal; depletion of p27Kip1 in MEF (mouse embryonic fibroblast) cells resulted in markedly elevated EGFR expression, a result reproducible with an Egfr promoter-luciferase reporter in both T24 and MEF cells, suggesting transcriptional repression of EGFR by p27Kip1. Indeed, p27Kip1 was found to regulate EGFR expression via the JNK (c-Jun N-terminal kinase)/c-Jun transcription factor: p27Kip1 deficiency activated JNK/c-Jun, whereas inhibition of JNK/c-Jun by dominant-negative mutants dramatically repressed Egfr transcription. Furthermore, the proximal promoter of the Egfr gene was crucial for its transcription, where the recruiting activity of c-Jun was much greater in p27Kip1-/- cells than in p27Kip1+/+ cells. Introduction of GFP-p27Kip1 into T24T cells suppressed JNK/c-Jun activation, EGFR expression and anchorage-independent growth. The results of the present study demonstrate that p27Kip1 suppresses JNK/c-Jun activation and EGFR expression in MEFs and human bladder cancer cells, and the results obtained are consistent with those from human cancer specimens. The present study provides new insights into p27Kip1 suppression of cancer cell growth, migration and metastasis.
Related JoVE Video
[Identification of three novel frameshift mutations in the RUNX2 gene in three sporadic Chinese cases with cleidocranial dysplasia].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 08-15-2014
Show Abstract
Hide Abstract
To investigate the molecular etiology of three patients with sporadic cleidocranial dysplasia (CCD) and to provide genetic counseling and prenatal diagnosis for the family members based on the identified mutations.
Related JoVE Video
Gadolinium oxalate derivatives with enhanced magnetocaloric effect via ionothermal synthesis.
Inorg Chem
PUBLISHED: 08-12-2014
Show Abstract
Hide Abstract
Two new oxalate-bridged Gd(III) coordination polymers, namely, (choline)[Gd(C2O4)(H2O)3Cl]Cl·H2O (1) and [Gd(C2O4)(H2O)3Cl] (2), were first obtained ionothermally by using a deep eutectic solvent (DES). The magnetic studies and heat capacity measurements reveal that the two-dimensional Gd(III)-based coordination polymer of 2 has the higher magnetic density and exhibits a larger cryogenic magnetocaloric effect (MCE) (?S(m) = 48 J kg(-1) K(-1) for ?H = 7 T at 2.2 K).
Related JoVE Video
CRISPR Primer Designer: Design primers for knockout & chromosome imaging CRISPR-Cas system.
J Integr Plant Biol
PUBLISHED: 08-10-2014
Show Abstract
Hide Abstract
Clustered regularly interspaced short palindromic repeats - CRISPR associated system enables biologists to edit genome precisely and provides a powerful tool for perturbing endogenous gene regulation, modulation of epigenetic markers and genome architecture. However, there are concerns rose about the specificity of the system, especially the usages of knocking out a gene. Previous designing tools either were mostly built-in websites or ran as command-line program, and none of them ran locally and acquired a user-friendly interface. In addition, with the development of CRISPR derived-systems, such as chromosome imaging, there were still no tools helping users to generate specific end-user spacers. We here presented CRISPR Primer Designer for researchers to design primers for CRISPR applications. The program has a user-friendly interface, and can analyze the BLAST results by using multiple parameters and score for each candidate spacers, generate the primers when using a certain plasmid. In addition, CRISPR Primer Designer runs locally and can be used to search spacer clusters, and exports primers for CRISPR-Cas system based chromosome imaging system.
Related JoVE Video
Complete sequence and characterization of mitochondrial DNA genome of Channa asiatica (Perciformes: Channidae).
Mitochondrial DNA
PUBLISHED: 08-08-2014
Show Abstract
Hide Abstract
Abstract The complete nucleotide sequence of Channa asiatica mitochondrial (mtDNA) genome was determined in this study. The genome sequence (GenBank accession number KJ930190) was 16,550 base pairs in length, and the gene content and organization on the mitochondrial genome were similar to the other Channa fishes. The overall base composition of C. asiatica mitogenome is 29.4% A, 26.3% T, 15.3% G, 29.0% C, with a high A?+?T content of 55.7%. The mitochondrial sequence could provide useful genetic information for studying the molecular identification, population genetics, phylogenetic analysis and conservation genetics.
Related JoVE Video
[Analysis of clinical and laboratory features of 217 pediatric hemophagocytic lymphohistiocytosis].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 07-24-2014
Show Abstract
Hide Abstract
To investigate the incidence, clinical symptoms, signs and laboratory features of childhood hemophagocytic lymphohistiocytosis (HLH) in China.
Related JoVE Video
Polyanion binding accelerates the formation of stable and low-toxic aggregates of ALS-linked SOD1 mutant A4V.
Proteins
PUBLISHED: 07-13-2014
Show Abstract
Hide Abstract
The toxic property thus far shared by both ALS-linked SOD1 variants and wild-type SOD1 is an increased propensity to aggregation. However, whether SOD1 oligomers or aggregates are toxic to cells remains to be well defined. Moreover, how the toxic SOD1 species are removed from intra- and extracellular environments also needs to be further explored. The DNA binding has been shown to be capable of accelerating the aggregatio\n of wild-type and oxidized SOD1 forms under acidic and neutral conditions. In this study, we explore the binding of DNA and heparin, two types of essential life polyanions, to A4V, an ALS-linked SOD1 mutant, under acidic conditions, and its consequences. The polyanion binding alters the A4V conformation, neutralizes its local positive charges, and increases its local concentrations along the polyanion chain, which are sufficient to lead to acceleration of the pH-dependent A4V aggregation. The accelerated aggregation, which is ascribed to the polyanion binding-mediated removal or shortening of the lag phase in aggregation, contributes to the formation of amorphous A4V nanoparticles. The prolonged incubation with polyanions not only results in the complete conversion of likely soluble toxic A4V oligomers into non- and low-toxic SDS-resistant aggregates, but also increases their stability. Although this is only an initial step toward reducing the toxicity of SOD1 mutants, the accelerating role of polyanions in protein aggregation might become one of the rapid pathways that remove toxic forms of SOD1 mutants from intra- and extracellular environments. Proteins 2014; 82:3356-3372. © 2014 Wiley Periodicals, Inc.
Related JoVE Video
Mandibuloacral dysplasia type A-associated progeria caused by homozygous LMNA mutation in a family from Southern China.
BMC Pediatr
PUBLISHED: 05-19-2014
Show Abstract
Hide Abstract
Mandibuloacral dysplasia type A (MADA) is a rare autosomal recessive disorder, characterized by growth retardation, skeletal abnormality with progressive osteolysis of the distal phalanges and clavicles, craniofacial anomalies with mandibular hypoplasia, lipodystrophy and mottled cutaneous pigmentation. Some patients may show progeroid features. MADA with partial lipodystrophy, more marked acral, can be caused by homozygous or compound heterozygous mutation in the gene encoding lamin A and lamin C (LMNA). MADA and Hutchinson-Gilford progeria syndrome are caused by the same gene and may represent a single disorder with varying degrees of severity. MAD patients characterized by generalized lipodystrophy (type B) affecting the face as well as extremities and severe progressive glomerulopathy present heterozygous compound mutations in the ZMPSTE24 gene.
Related JoVE Video
Immobility responses between mouse strains correlate with distinct hippocampal serotonin transporter protein expression and function.
Int. J. Neuropsychopharmacol.
PUBLISHED: 05-15-2014
Show Abstract
Hide Abstract
Mouse strain differences in immobility and in sensitivity to antidepressants have been observed in the forced swimming test (FST) and the tail suspension test (TST). However, the neurotransmitter systems and neural substrates that contribute to these differences remain unknown. To investigate the role of the hippocampal serotonin transporter (5-HTT), we measured baseline immobility and the immobility responses to fluoxetine (FLX) in the FST and the TST in male CD-1, C57BL/6, DBA and BALB/c mice. We observed strain differences in baseline immobility time, with CD-1 mice showing the longest and DBA mice showing the shortest. In contrast, DBA and BALB/c mice showed the highest sensitivity to FLX, whereas CD-1 and C57BL/6 mice showed the lowest sensitivity. Also we found strain differences in both the total 5-HTT protein level and the membrane-bound 5-HTT level (estimated by V max) as follows: DBA>BALB/c>CD-1=C57BL/6. The uptake efficiency of the membrane-bound 5-HTT (estimated by 1/K m) was highest in DBA and BALB/c mice and lowest in CD-1 and C57BL/6 mice. A correlation analysis of subregions within the hippocampus revealed that immobility time was negatively correlated with V max and positively correlated with K m in the hippocampus. Therefore a higher uptake capacity of the membrane-bound 5-HTT in the hippocampus was associated with lower baseline immobility and greater sensitivity to FLX. These results suggest that alterations in hippocampal 5-HTT activity may contribute to mouse strain differences in the FST and the TST.
Related JoVE Video
Nuclear factor of activated T cells 5 maintained by Hotair suppression of miR-568 upregulates S100 calcium binding protein A4 to promote breast cancer metastasis.
Breast Cancer Res.
PUBLISHED: 05-13-2014
Show Abstract
Hide Abstract
IntroductionThe onset of distal metastasis, which underlies the high mortality of breast cancers, warrants substantial studies to depict its molecular basis. Nuclear factor of activated T cells 5 (NFAT5) is upregulated in various malignancies and is critically involved in migration and invasion of neoplastic cells. Nevertheless, the metastasis-related events potentiated by this transcriptional factor and the mechanism responsible for NFAT5 elevation in carcinoma cells remain to be fully elucidated.MethodsThe correlation of NFAT5 with breast cancer invasiveness was investigated in vitro and clinically. The genes transcriptionally activated by NFAT5 were probed and their roles in breast cancer progression were dissected. The upstream regulators of NFAT5 were studied with particular attempt to explore the involvement of non-coding RNAs, and the mechanism underlying the maintenance of NFAT5 expression was deciphered.ResultsIn metastatic breast cancers, NFAT5 promotes epithelial-mesenchymal transition (EMT) and invasion of cells by switching on the expression of the calcium binding protein S100A4, and facilitates the angiogenesis of breast epithelial cells and thus the development of metastases by transcriptionally activating vascular endothelial growth factor C (VEGF-C). NFAT5 is directly targeted by miR-568, which is in turn suppressed by the long non-coding RNA, Hotair, via a documented in trans gene silencing pattern, that is recruitment of the polycomb complex (Polycomb Repressive Complex 2; PRC2) and LSD1, and consequently methylation of histone H3K27 and demethylation of H3K4 on the miR-568 loci.ConclusionThis study unravels a detailed role of NFAT5 in mediating metastatic signaling, and provides broad insights into the involvement of Hotair, in particular, by transcriptionally regulating the expression of microRNA(s), in the metastasis of breast cancers.
Related JoVE Video
PEGylation alleviates the non-specific toxicities of Alpha-Momorcharin and preserves its antitumor efficacy in vivo.
Drug Deliv
PUBLISHED: 05-03-2014
Show Abstract
Hide Abstract
Abstract Alpha-Momorcharin (?-MMC) is a ribosome inactivating protein from Momordica charantia with anti-tumor activity. Previously, we had observed that modification of ?-MMC with polyethylene glycol (PEG) could reduce toxicity, but it also reduces its anti-tumor activity in vitro. This study aims to investigate whether the metabolism-extended properties of ?-MMC resulting from PEGylation could preserve its anti-tumor efficacy in vivo through pharmacokinetics and antitumor experiments. The pharmacokinetics experiments were conducted in rats using the TCA (Trichloroacetic Acid) method. Antitumor activity in vivo was investigated in murine mammary carcinoma (EMT-6) and human mammary carcinoma (MDA-MB-231) transplanted tumor mouse models. The results showed that PEGylation increased the plasma half-life of ?-MMC in rats from 6.2-7.5?h to 52-87?h. When administered at 1?mg/kg, ?-MMC-PEG and ?-MMC showed similar anti-tumor activities in vivo, with a T/C% of 38.56% for ?-MMC versus 35.43% for ?-MMC-PEG in the EMT-6 tumor model and 36.30% for ?-MMC versus 39.88% for ?-MMC-PEG in the MDA-MB-231 tumor model (p?>?0.05). Importantly, at the dose of 3?mg/kg, all the animals treated with ?-MMC died while the animals treated with ?-MMC-PEG exhibited only moderate toxic reactions, and ?-MMC-PEG exhibited improved anti-tumor efficacy with a T/C% (relative tumor growth rate) of 25.18% and 21.07% in the EMT-6 and MDA-MB-231 tumor models, respectively. The present study demonstrates that PEGylation extends the half-life of ?-MMC and alleviates non-specific toxicity, thereby preserving its antitumor efficacy in vivo, and a higher lever of dosage can be used to achieve better therapeutic efficacy.
Related JoVE Video
Evaluation of MYOC, ACAN, HGF, and MET as candidate genes for high myopia in a Han Chinese population.
Genet Test Mol Biomarkers
PUBLISHED: 04-25-2014
Show Abstract
Hide Abstract
To investigate the association between high myopia (HM) and single nucleotide polymorphisms (SNPs) in the myocilin (MYOC), hepatocyte growth factor (HGF), hepatocyte growth factor receptor (MET), and aggrecan (ACAN) genes in a Han Chinese population.
Related JoVE Video
Effects of GnRH antagonist on endometrial protein profiles in the window of implantation.
Proteomics
PUBLISHED: 04-17-2014
Show Abstract
Hide Abstract
GnRH antagonists can suppress luteinizing hormone and follicle-stimulating hormone (FSH), with less initial stimulatory effect and lower risk of ovarian hyperstimulation syndrome. The effects of GnRH antagonists on embryonic implantation remain controversial. To evaluate the effects of GnRH antagonists, endometrial tissues were biopsied from 12 women with intracytoplasmic sperm injection treatment, in which four subjects undergoing controlled ovulation stimulation with rFSH and GnRH antagonist, four subjects with a GnRH agonist long protocol, and four natural cycle controls. After iTRAQ quantification analysis, 24 proteins showed differential expression between natural cycle and agonist treatment group and 39 proteins between natural cycle and antagonist treatment group. A total of seven proteins demonstrated differential expression only in antagonist treatment group. Bioinformatic analysis implied these proteins can function in cell processes including angiogenesis, cell proliferation, apoptosis, cell migration, and immune response. Furthermore, GnRH antagonist suppressed the function of GNAS and ANPEP, which were important for endometrial functions. Immunohistochemical staining showed that ANPEP was mainly localized in the human endometrial stroma, while ACO2, CDC5L, and GNAS were mainly localized in the glands. This study could provide insights into the effect of GnRH antagonists on the endometrium, and help optimize the embryo implantation and improve the success rate for GnRH antagonist protocol.
Related JoVE Video
Loss of p27 upregulates MnSOD in a STAT3-dependent manner, disrupts intracellular redox activity and enhances cell migration.
J. Cell. Sci.
PUBLISHED: 04-11-2014
Show Abstract
Hide Abstract
Cell migration is a dynamic process that is central to a variety of physiological functions as well as disease pathogenesis. The modulation of cell migration by p27 (officially known as CDKN1B) has been reported, but the exact mechanism(s) whereby p27 interacts with downstream effectors that control cell migration have not been elucidated. By systematically comparing p27(+/+) mouse embryonic fibroblasts (MEFs) with genetically ablated p27(-/-) MEFs using wound-healing, transwell and time-lapse microscopic analyses, we provide direct evidence that p27 inhibits both directional and random cell migration. Identical results were obtained with normal and cancer epithelial cells using complementary knockdown and overexpression approaches. Additional studies revealed that overexpression of manganese superoxide dismutase (MnSOD, officially known as SOD2) and reduced intracellular oxidation played a key role in increased cell migration in p27-deficient cells. Furthermore, we identified signal transducer and activator of transcription 3 (STAT3) as the transcription factor responsible for p27-regulated MnSOD expression, which was further mediated by ERK- and ATF1-dependent transactivation of the cAMP response element (CRE) within the Stat3 promoter. Collectively, our data strongly indicate that p27 plays a crucial negative role in cell migration by inhibiting MnSOD expression in a STAT3-dependent manner.
Related JoVE Video
Quantitative proteomic study of myocardial mitochondria in urea transporter B knockout mice.
Proteomics
PUBLISHED: 04-04-2014
Show Abstract
Hide Abstract
In previous research, we showed that 16-week-old urea transporter B (UT-B) null mice have an atrial-ventricular conduction block, and hypothesized myocardial mitochondrial dysfunction. To investigate the mechanism of this block, we examined the proteomic differences in the myocardial mitochondria of UT-B null and wild-type mice with nanoscale LC-MS/MS. Of 26 proteins clearly downregulated in the UT-B null mice, 15 are involved in complexes I, III, IV, and V of the respiratory chain, which would strongly reduce the activity of the electron transport chain. Excess electrons from complexes I and III pass directly to O2 to generate ROS and deplete ROS-scavenging enzymes. Myocardial intracellular ROS were significantly higher in UT-B null mice than in wild-type mice (p < 0.01), constituting an important cause of oxidative stress injury in the myocardia of UT-B null mice. The mitochondrial membrane potential (??m) was also lower in UT-B null mice than in wild-type mice (p < 0.05), causing oxidative phosphorylation dysfunction of complex V and insufficient ATP in the myocardial cells of UT-B null mice. HADHA (a trifunctional protein) and HSP60 were also downregulated in the UT-B null myocardial mitochondria. These results confirm that mitochondrial dysfunction underlies the pathogenesis of the atrial-ventricular conduction block in UT-B null mice.
Related JoVE Video
Serum albumin as a significant prognostic factor in patients with malignant pleural mesothelioma.
Tumour Biol.
PUBLISHED: 04-03-2014
Show Abstract
Hide Abstract
Our aim was to evaluate the prognostic role of the pretreatment serum albumin level in patients with malignant pleural mesothelioma (MPM) receiving platinum-based systemic chemotherapy. From 1995 to 2013, a total of 97 patients receiving platinum-based systemic chemotherapy for newly diagnosed MPM were enrolled. All clinical information and laboratory results were retrospectively collected from the medical records. The Kaplan-Meier method was used to calculate survival. The Cox proportional hazards model was used to identify significant independent prognostic factors for predicting survival. In total, 34 of the 97 patients (35.1 %) had hypoalbuminaemia (albumin ? 35 g/l). The 1-year overall survival rate was 44.1 % for patients with hypoalbuminaemia and 72.0 % for patients with a normal albumin level. Multivariate analysis indicated that pretreatment albumin was an independent prognostic factor in MPM. Patients with hypoalbuminaemia had a greater risk of death than those with a normal albumin level [hazard ratio (HR) 1.778; 95 % confidence interval (CI) 1.504-2.998; P = 0.031]. When albumin was entered as a continuous variable in the Cox regression model, the HR of death was significantly decreased by 9.8 % (95 % CI 0.851-0.956) for each 1-g/l increment. The pretreatment serum albumin level is a simple, inexpensive and easily measurable marker with prognostic significance in MPM patients treated with platinum-based systemic chemotherapy.
Related JoVE Video
Insulin-like growth factor 1 can promote proliferation and osteogenic differentiation of human dental pulp stem cells via mTOR pathway.
Dev. Growth Differ.
PUBLISHED: 03-16-2014
Show Abstract
Hide Abstract
Insulin-like growth factor 1 (IGF-1) is a multifunctional peptide that can enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). However, it remains unclear whether IGF-1 can promote osteogenic differentiation of human dental pulp stem cells (DPSCs). In our study, DPSCs were isolated from the impacted third molars, and treated with IGF-1. Osteogenic differentiation abilities were investigated. We found that IGF-1 activated the mTOR signaling pathway during osteogenic differentiation of DPSCs. IGF-1 also increased the expression of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osterix (OSX) and collagen type I (COL I) during this process. Rapamycin, an mTOR inhibitor, blocked osteogenic differentiation induced by IGF-1. Meanwhile, CCK-8 assay and flow cytometry results demonstrated that 10-200 ng/mL IGF-1 could enhance proliferation ability of DPSCs and 100 ng/mL was the optimal concentration. In summary, IGF-1 could promote proliferation and osteogenic differentiation of DPSCs via mTOR pathways, which might have clinical implications for osteoporosis.
Related JoVE Video
Environmental-confinement-induced stability enhancement of chiral molecules.
Chemphyschem
PUBLISHED: 03-07-2014
Show Abstract
Hide Abstract
We computationally study the transition process of a chiral difluorobenzo[c]phenanthrene (DFBcPh) molecule within non-polar fullerene C(260) to explore the confinement effect. We find blue-shifts in the infrared and Raman spectra of the molecule inside the fullerene relative to those of isolated systems. Six types of spectrum features of the molecule appear in the 0-60 cm(-1) band. Interestingly, the energy barrier of the chiral transformation of the molecule is elevated by 15.88 kcal mol(-1) upon the confinement by the fullerene, indicating improvement in the stability of the enantiomers. The protection by C(260) lowers the highest occupied molecular orbital energy level and lifts the lowest unoccupied molecular orbital energy level of the chiral molecule such that the chiral molecule is further chemically stabilized. We concluded that the confinement environment has an impact at the nanoscale on the enantiomer transformation process of the chiral molecule.
Related JoVE Video
Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.
Hum. Genet.
PUBLISHED: 03-06-2014
Show Abstract
Hide Abstract
C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multiethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7,570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women's Health Initiative (WHI) and KORA studies. We observed array-wide significance (p < 2.2 × 10(-6)) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p = 2.0 × 10(-6); CRP, p = 4.2 × 10(-71); APOE, p = 1.6 × 10(-6)). The fourth significant locus, CD36 (p = 1.6 × 10(-6)), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding (p = 1.8 × 10(-5)) in an independent sample of 8,041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance (p = 1.5 × 10(-10)). In the race-combined meta-analyses, 13 loci reached significance, including ten (CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one (ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected (RPS6KB1, p = 2.0 × 10(-6); CD36, p = 1.4 × 10(-6)). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent.
Related JoVE Video
Structural and electronic properties of uranium-encapsulated Au?? cage.
Sci Rep
PUBLISHED: 01-20-2014
Show Abstract
Hide Abstract
The structural properties of the uranium-encapsulated nano-cage U@Au14 are predicted using density functional theory. The presence of the uranium atom makes the Au14 structure more stable than the empty Au14-cage, with a triplet ground electronic state for U@Au14. Analysis of the electronic structure shows that the two frontier single-occupied molecular orbital electrons of U@Au14 mainly originate from the 5f shell of the U atom after charge transfer. Meanwhile, the bonding orbitals and charge population indicate that the designed U@Au14 nano-cage structure is stabilized by ionocovalent interactions. The current findings provide theoretical basis for future syntheses and further study of actinide doped gold nanoclusters, which might subsequently facilitate applications of such structure in radio-labeling, nanodrug carrier and other biomedical applications.
Related JoVE Video
Identification of novel mutations of PKD1 gene in Chinese patients with autosomal dominant polycystic kidney disease by targeted next-generation sequencing.
Clin. Chim. Acta
PUBLISHED: 01-17-2014
Show Abstract
Hide Abstract
Mutations of PKD1 and PKD2 accounted for the most cases of autosomal dominant polycystic kidney disease (ADPKD). The presence of the large transcript, numerous exons and complex reiterated regions within the gene has significantly complicated the analysis of PKD1 with routine PCR-based approaches.
Related JoVE Video
Ubiquitin-activating enzyme E1 inhibitor PYR41 attenuates angiotensin II-induced activation of dendritic cells via the I?Ba/NF-?B and MKP1/ERK/STAT1 pathways.
Immunology
PUBLISHED: 01-17-2014
Show Abstract
Hide Abstract
The activation of dendritic cells (DCs) is necessary to initiate immune responses. Angiotensin II (Ang II) can enhance the maturation and activation of DCs, but the mechanisms are still unclear. Ubiquitin-activating enzyme (E1/Uba1) is the common first step in ubiquitylation, which decides whether or not the modified protein is ultimately degraded by the proteasome. This study aimed to investigate the role of E1 in Ang II-induced activation of DCs and the underlying mechanisms. First, we showed that Ang II stimulation significantly up-regulated E1 expression in DCs. Moreover, Ang II treatment markedly induced phenotypic maturation, the secretion of cytokines and the immunostimulatory capacity of DCs. In contrast, inhibition of E1 by a small molecule inhibitor, 4 [4-(5-nitro-furan-2-ylmethylene)-3, 5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (PYR41), markedly attenuated these effects. Mechanistically, PYR41 treatment markedly decreased K63-linked ubiquitination of tumour necrosis factor receptor-associated factor 6 and nuclear factor-?B essential modulator, inhibited proteasomal degradation of nuclear factor-?B inhibitor ? and mitogen-activated protein kinase phosphatase 1 thereby resulting in activation of nuclear factor-?B, extracellular signal-regulated kinase 1/2 and signal transducer and activator of transcription 1 signalling pathways in DCs induced by Ang II. Taken together, our results demonstrate a novel role of E1 in Ang II-induced activation of DCs, and inhibition of E1 activity might be a potential therapeutic target for DC-mediated autoimmune diseases.
Related JoVE Video
Subregion-specific decreases in hippocampal serotonin transporter protein expression and function associated with endophenotypes of depression.
Hippocampus
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
Stress influences the development of depression, and depression is associated with structural and functional changes in the hippocampus. The current study sought to determine whether chronic corticosteroid (CORT) treatment influences serotonin transporter (5-HTT) protein expression and function in the CA1, CA3, and dentate gyrus (DG) subregions of the hippocampus. Male CD-1 mice were subcutaneously injected with CORT at a dose of 20 mg/kg once daily for 3 weeks. Behavioral state was assessed using sucrose preference, physical state of the coat, forced swimming test, and tail suspension test. We then determine 5-HTT protein expression and synaptosomal 5-HT uptake in the CA1, CA3 and DG subregions. CORT treatment induced anhedonia and behavioral despair, two core endophenotypes of clinical depression; 5-HTT protein expression levels and synaptosomal 5-HT uptake were both decreased in a subregion-specific manner, with the greatest decrease observed in the DG, a moderate decrease in the CA3, and the CA1 showed no apparent change. In addition, a reduction in tissue mass was detected in the DG following the CORT treatment. These data indicate that subregion-specific decreases in hippocampal 5-HTT protein expression and function are associated with endophenotypes of depression.
Related JoVE Video
Pathological and microbiological findings from mortality of the Chinese giant salamander (Andrias davidianus).
Arch. Virol.
PUBLISHED: 01-03-2014
Show Abstract
Hide Abstract
The Chinese giant salamander, Andrias davidianus, is a nationally protected and cultured species in China. Recently, a severe epizootic occurred in cultured Chinese giant salamanders in Hubei, Hunan, Sichuan, Shaanxi, and Zhejiang provinces of China, causing substantial economic losses. The typical clinical signs of diseased larval animals were jaw and abdominal swelling and subcutaneous hemorrhaging. Diseased adult animals exhibited skin hemorrhages, ulceration of the hind limbs, and multiple hemorrhagic spots in the visceral organs. Histopathological observation indicated tissue necrosis and cytoplasmic inclusions in the spleen, liver and kidney, suggestive of viral disease. A viral agent was isolated from affected tissues in cell culture. The virus was determined to be pathogenic after experimental infection. Electron microscopy revealed iridovirus-like virions with a size of 140-180 nm in diameter inside the kidney of naturally infected animals and in cell culture. The major capsid protein (MCP) of the virus exhibited 98-99 % sequence identity to ranaviruses. Additionally, phylogenetic analysis indicated that the virus belonged to the genus Ranavirus. Comparative analysis of the MCP gene sequence with those of other viruses previously isolated from Chinese giant salamanders revealed that these isolates were highly similar, although a few variations were observed. The virus was preliminarily named Chinese giant salamander iridovirus (GSIV).
Related JoVE Video
Proliferative ductular reactions correlate with hepatic progenitor cell and predict recurrence in HCC patients after curative resection.
Cell Biosci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Ductular reactions (DRs) are well documented in many acute and chronic liver disease.The DRs are thought to be the transit amplifying cells deriving from activation of the stem/progenitor cell compartments of the liver. The aim of this study was to examine the presence of proliferative index of DR (PI-DR) and HPC markers' expression in HCCs after curative hepatectomy, as well as their relationship with clinicopathological features and prognosis.
Related JoVE Video
Sequence, structural and expression divergence of duplicate genes in the bovine genome.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Gene duplication is a widespread phenomenon in genome evolution, and it has been proposed to serve as an engine of evolutionary innovation. In the present study, we performed the first comprehensive analysis of duplicate genes in the bovine genome. A total of 3131 putative duplicated gene pairs were identified, including 712 cattle-specific duplicate gene pairs unevenly distributed across the genome, which are significantly enriched for specific biological functions including immunity, growth, digestion, reproduction, embryonic development, inflammatory response, and defense response to bacterium. Around 97.1% (87.8%) of (cattle-specific) duplicate gene pairs were found to have distinct exon-intron structures. Analysis of gene expression by RNA-Seq and sequence divergence (synonymous or non-synonymous) revealed that expression divergence is correlated with sequence divergence, as has been previously observed in other species. This analysis also led to the identification of a subset of cattle-specific duplicate gene pairs exhibiting very high expression divergence. Interestingly, further investigation revealed a significant relationship between structural and expression divergence while controlling for the effect of synonymous sequence divergence. Together these results provide further insight into duplicate gene sequence and expression divergence in cattle, and their potential contributions to phenotypic divergence.
Related JoVE Video
Mesenchymal stem cells contribute to the chemoresistance of hepatocellular carcinoma cells in inflammatory environment by inducing autophagy.
Cell Biosci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Mesenchymal stem cells (MSCs) have been reported to play an important role in tumor growth. Inflammation is an important feature of hepatocellular carcinoma (HCC). Certain inflammatory cytokines produced in tumor microenvironment modulate functional activities of MSCs. At the present time, however, the role of MSCs in the development of HCC cell resistance to chemotherapy in the inflammatory microenvironment during tumor growth has not yet been identified.
Related JoVE Video
MiR-568 inhibits the activation and function of CD4+ T cells and Treg cells by targeting NFAT5.
Int. Immunol.
PUBLISHED: 12-19-2013
Show Abstract
Hide Abstract
CD4(+) T cells play critical roles in orchestrating adaptive immune responses. Their activation and proliferation are critical steps that occur before they execute their biological functions. Despite the important role of this process, the underlying molecular events are not fully understood. MicroRNAs (miRNAs) have been shown to play important roles in lymphocyte development and function. However, the miRNAs that regulate T-cell differentiation, activation and proliferation are still largely unknown. In our previous study, using a miRNA array, we found that several miRNAs (including miR-202, 33b, 181c, 568 and 576) are differentially expressed between resting and activated CD4(+) T cells. In this study, we focused on the function of miR-568 during CD4(+) T-cell activation. We showed that the expression level of miR-568 decreased during the activation of T cells, including Jurkat cells and human peripheral blood CD4(+) T cells. When Jurkat or human peripheral blood CD4(+) T cells were transfected with miR-568 mimics, cell activation was significantly inhibited, as shown by the inhibited expression of activation markers such as CD25, CD69 and CD154; decreased IL-2 production; and inhibited cell proliferation. Using software predictions and confirmatory experiments, we demonstrated that nuclear factor of activated T cells 5 (NFAT5) is a target of miR-568. Treg cells are an important CD4(+) T-cell subpopulation, so we also evaluated the function of miR-568 in Treg-cell activation and differentiation. We showed that the miR-568 level decreased, while the NFAT5 protein level increased during CD4(+)CD25(+) Treg-cell activation, and the transfection of miR-568 mimics inhibited the NFAT5 expression, inhibited the production of both TGF-? and IL-10 and also inhibited the proliferation of Treg cells. Our further study showed that over-expression of miR-568 can inhibit Treg-cell differentiation and can inhibit the suppressive effect of these cells on effector cells. In addition, inhibition of NFAT5 by siRNA-mediated knockdown can inhibit the activation and differentiation of Treg cells. These findings reveal that miR-568 can inhibit the activation and function of both CD4(+) T cells and Treg cells by targeting NFAT5. Since miR-568 plays an important role in both CD4(+) T cells and Treg cells, these findings may provide leads for the development of novel treatments for human inflammatory and autoimmune diseases.
Related JoVE Video
[Clinical characterization of patients with Danon disease].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 11-29-2013
Show Abstract
Hide Abstract
To analyze the clinical characterization of Danon disease caused by the mutation of lysosome-associated membrane protein-2 (LAMP-2) gene.
Related JoVE Video
[Analysis of the efficacy of postoperative radiotherapy in gallbladder cancer].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 11-22-2013
Show Abstract
Hide Abstract
To summarize the experiences in gallbladder cancer treatment, evaluate the efficacy of postoperative radiotherapy, and investigate the method of improving the survival of gallbladder cancer patients.
Related JoVE Video
Analysis of Acidic Endogenous Phytohormones in Grapes by Using Online Solid-Phase Extraction Coupled with LC-MS/MS.
J Chromatogr Sci
PUBLISHED: 11-07-2013
Show Abstract
Hide Abstract
Phytohormones play important roles in regulating numerous plant physiological and developmental processes, even during the postharvest storage period. In order to determine the functions and changes of gibberellins acid (GA3), indoleacetic acid (IAA), abscisic acid (ABA), indolebutyric acid (IBA) and jasmonic acid (JA) in grape berries during storage, an ultrasensitive method based on direct injection online solid-phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. Grape berries were extracted with cold methanol. After centrifugation, the supernatants were concentrated with a vacuum centrifugal concentrator and injected into an online solid-phase extraction column. After the cleanup procedure, the analytes were determined by LC-MS/MS. The results showed that the linearity of the proposed method was 10-210 µg kg(-1) for ABA, 20-200 µg kg(-1) for IBA, 15-320 µg kg(-1) for IAA, 20-320 µg kg(-1) for GA3 and 3.0-90.0 µg kg(-1) for JA. The limits of detection of the method were 0.71, 2.79, 0.94, 0.39 and 0.57 µg kg(-1), respectively. The proposed method was successfully applied to the analysis of endogenous phytohormones in grape berries during the postharvest storage period.
Related JoVE Video
An egocentric vision based assistive co-robot.
IEEE Int Conf Rehabil Robot
PUBLISHED: 11-05-2013
Show Abstract
Hide Abstract
We present the prototype of an egocentric vision based assistive co-robot system. In this co-robot system, the user is wearing a pair of glasses with a forward looking camera, and is actively engaged in the control loop of the robot in navigational tasks. The egocentric vision glasses serve for two purposes. First, it serves as a source of visual input to request the robot to find a certain object in the environment. Second, the motion patterns computed from the egocentric video associated with a specific set of head movements are exploited to guide the robot to find the object. These are especially helpful for quadriplegic individuals who do not have needed hand functionality for interaction and control with other modalities (e.g., joystick). In our co-robot system, when the robot does not fulfill the object finding task in a pre-specified time window, it would actively solicit user controls for guidance. Then the users can use the egocentric vision based gesture interface to orient the robot towards the direction of the object. After that the robot will automatically navigate towards the object until it finds it. Our experiments validated the efficacy of the closed-loop design to engage the human in the loop.
Related JoVE Video
Irisin Stimulates Browning of White Adipocytes through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling.
Diabetes
PUBLISHED: 10-22-2013
Show Abstract
Hide Abstract
The number and activity of brown adipocytes are linked to the ability of mammals to resist body fat accumulation. In some conditions, certain white adipose tissue (WAT) depots are readily convertible to a brown-like statewhich is associated with weight loss. Irisin, a newly identified hormone, is secreted by skeletal muscles into circulation and promotes WAT "browning" with unknown mechanisms. In the current study, we demonstrated in mice that recombinant irisin decreased the bodyweight and improved glucose homeostasis. We further showed that irisin upregulated UCP-1 (a regulator of thermogenic capability of brown fat) expression. This effect was possibly mediated by irisin induced phosphorylation of p38 MAPK and ERK signaling pathway. Inhibition of the p38 MAPK by SB203580 and ERK by U0126 abolished the upregulatory effect of irisin on UCP-1. In addition, irisin also promoted the expression of betatrophin, another newly identified hormone that promotes pancreatic beta cell proliferation and improves glucose tolerance. In summary, our data suggest that irisin can potentially prevent obesity and associated type 2 diabetes by stimulating expression of WAT browning-specific genes via p38 MAPK and ERK pathway.
Related JoVE Video
Modification of carbon nanotube transparent conducting films for electrodes in organic light-emitting diodes.
Nanotechnology
PUBLISHED: 10-02-2013
Show Abstract
Hide Abstract
Single-walled carbon nanotube (SWCNT) transparent conducting films (TCFs) were fabricated for the electrodes of organic light-emitting diodes (OLEDs); three types of film were studied. The as-prepared SWCNT TCFs displayed a relatively low sheet resistance of 82.6 ?/sq at 80.7 T% with a relatively large surface roughness of 30 nm. The TCFs were top-coated with poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) to obtain PEDOT:PSS-coated TCFs. The PEDOT:PSS cover improved the conductivity and decreased the surface roughness to 12 nm at the cost of film transmittance. The SWCNT TCFs mixed with PEDOT:PSS (PM-TCFs) exhibited a high conductivity (70.6 ?/sq at 81 T%) and a low surface roughness (3 nm) and were thus selected as the best TCFs for OLEDs. Blue flexible OLEDs with 4,4-bis(2,2-diphenylvinyl)-1,1-biphenyl (Dpvbi) as the emitting layer were fabricated on TCFs with the same structures to evaluate the performances of the different types of SWCNT films for use in OLEDs. Of these three types of OLEDs, the PM-TCF devices exhibited the optimal performance with a maximum luminance of 2587 cd m(-2) and a current efficiency of 5.44 cd A(-1). This result was explored using field-emission scanning electron microscopy and atomic force microscopy to further study the mechanisms that are involved in applying SWCNT TCFs to OLEDs.
Related JoVE Video
[Effect of PEGylation of alpha-Momorcharin against its hepatotoxicity in rats].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 09-25-2013
Show Abstract
Hide Abstract
To explore the effect of PEGylation of alpha-Momorcharin (alpha-MMC), one of ribosome-inactivating proteins from bitter melon seed, against its hepatotoxicity in rats.
Related JoVE Video
Signatures in vibrational and UV-visible absorption spectra for identifying cyclic hydrocarbons by graphene fragments.
Nanoscale
PUBLISHED: 09-24-2013
Show Abstract
Hide Abstract
To promote possible applications of graphene in molecular identification based on stacking effects, in particular in recognizing aromatic amino acids and even sequencing nucleobases in life sciences, we comprehensively study the interaction between graphene segments and different cyclic organic hydrocarbons including benzene (C6H6), cyclohexane (C6H12), benzyne (C6H4), cyclohexene (C6H10), 1,3-cyclohexadiene (C6H8(1)) and 1,4-cyclohexadiene (C6H8(2)), using the density-functional tight-binding (DFTB) method. Interestingly, we find obviously different characteristics in Raman vibrational and ultraviolet visible absorption spectra of the small molecules adsorbed on the graphene sheet. Specifically, we find that both spectra involve clearly different characteristic peaks, belonging to the different small molecules upon adsorption, with the ones of ionized molecules being more substantial. Further analysis shows that the adsorptions are almost all due to the presence of dispersion energy in neutral cases and involve charge transfer from the graphene to the small molecules. In contrast, the main binding force in the ionic adsorption systems is the electronic interaction. The results present clear signatures that can be used to recognize different kinds of aromatic hydrocarbon rings on graphene sheets. We expect that our findings will be helpful for designing molecular recognition devices using graphene.
Related JoVE Video
Toll-like receptor-2 ligand peptidoglycan upregulates expression and ubiquitin ligase activity of CHIP through JNK pathway.
Cell. Physiol. Biochem.
PUBLISHED: 09-16-2013
Show Abstract
Hide Abstract
Peptidoglycan (PGN) is a component of cell wall in Gram-positive bacteria that stimulates inflammatory responses through Toll-like receptor 2 (TLR2). The carboxyl terminus of constitutive heat shock cognate 70 (HSC70)-interacting protein (CHIP, also known as Stub1) is a U-box-type E3 ubiquitin ligase, which plays an important role in protein quality control and inflammation through ubquitin-mediated proteasomal degradation. However, it is unclear whether TLR2 agonist PGN regulates the expression and activation of CHIP.
Related JoVE Video
Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes.
Int. J. Mol. Med.
PUBLISHED: 09-02-2013
Show Abstract
Hide Abstract
There are statistical data indicating that diabetes is a risk factor for Parkinsons disease (PD). Methylglyoxal (MG), a biologically reactive byproduct of glucose metabolism, the levels of which have been shown to be increase in diabetes, reacts with dopamine to form 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ); this formation may provide further insight into the connection between PD and diabetes. In this study, we investigated the role of ADTIQ in these two diseases to determine in an aim to enhance our understanding of the link between PD and diabetes. To this end, a cell model of hyperglycemia and a rat model of diabetes were established. In the cell model of hyperglycemia, compared with the control group, the elevated glucose levels promoted free hydroxyl radical formation (p<0.01). An ADTIQ assay was successfully developed and ADTIQ levels were detected and quantified. The levels of its precursors, MG and dopamine (DA), were determined in both the cell model of hyperglycemia and the rat model of diabetes. The proteins related to glucose metabolism were also assayed. Compared with the control group, ADTIQ and MG levels were significantly elevated not only in the cell model of hyperglycemia, but also in the brains of rats with diabetes (p<0.01). Seven key enzymes from the glycolytic pathway were found to be significantly more abundant in the brains of rats with diabetes. Moreover, it was found that adenosine triphosphate (ATP) synthase and superoxide dismutase (SOD) expression levels were markedly decreased in the rats with diabetes compared with the control group. Therefore, ADTIQ expression levels were found to be elevated under hyperglycemic conditions. The results reported herein demonstrate that ADTIQ, which is derived from MG, the levels of which areincreased in diabetes, may serve as a neurotoxin to dopaminergic neurons, eventually leading to PD.
Related JoVE Video
Mla- and Rom1-mediated control of microRNA398 and chloroplast copper/zinc superoxide dismutase regulates cell death in response to the barley powdery mildew fungus.
New Phytol.
PUBLISHED: 08-26-2013
Show Abstract
Hide Abstract
Barley (Hordeum vulgare L.) Mildew resistance locus a (Mla) confers allele-specific interactions with natural variants of the ascomycete fungus Blumeria graminis f. sp. hordei (Bgh), the causal agent of powdery mildew disease. Significant reprogramming of Mla-mediated gene expression occurs upon infection by this obligate biotrophic pathogen. We utilized a proteomics-based approach, combined with barley mla, required for Mla12 resistance1 (rar1), and restoration of Mla resistance1 (rom1) mutants, to identify components of Mla-directed signaling. Loss-of-function mutations in Mla and Rar1 both resulted in the reduced accumulation of chloroplast copper/zinc superoxide dismutase 1 (HvSOD1), whereas loss of function in Rom1 re-established HvSOD1 levels. In addition, both Mla and Rom1 negatively regulated hvu-microRNA398 (hvu-miR398), and up-regulation of miR398 was coupled to reduced HvSOD1 expression. Barley stripe mosaic virus (BSMV)-mediated over-expression of both barley and Arabidopsis miR398 repressed accumulation of HvSOD1, and BSMV-induced gene silencing of HvSod1 impeded Mla-triggered H2 O2 and hypersensitive reaction (HR) at barley-Bgh interaction sites. These data indicate that Mla- and Rom1-regulated hvu-miR398 represses HvSOD1 accumulation, influencing effector-induced HR in response to the powdery mildew fungus.
Related JoVE Video
Wnt/?-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway.
Mol. Cell. Biochem.
PUBLISHED: 08-14-2013
Show Abstract
Hide Abstract
Recent studies have shown that allogeneic bone marrow (BM)-mesenchymal stem cell transplantation (MSCT) appears to be effective in systemic lupus erythematosus (SLE) patients and lupus-prone mice, contrary to studies in syngeneic BM-MSCT. These studies indicated that the abnormalities of BM-MSCs may be involved in the pathogenesis of SLE. Our studies and other previous studies have revealed that BM-MSCs from SLE patients exhibited early signs of senescence, such as flattened morphology, slow proliferation, increased senescence-associated ?-galactosidase (SA-?-gal) activity, and so on. However, the mechanisms by which these cells senescences were still unclear. Previous studies have demonstrated that Wnt/?-catenin signaling plays an important role in stem cell senescence. In the current study, we investigated whether Wnt/?-catenin signaling mediates the senescence of BM-MSCs from SLE patients. We have found that Wnt/?-catenin signaling and the p53/p21 pathway were significantly hyperactivated in senescent SLE BM-MSCs. Treatment with 100 ng/mL Dickkopf-1 (DKK1), a Wnt/?-catenin signaling inhibitor or ?-catenin siRNA for 48 h could reverse the senescent features of SLE BM-MSCs. Additionally, the expression levels of p53 and p21 were reduced in treated-SLE BM-MSCs compared with the untreated group. In summary, our study indicated that Wnt/?-catenin signaling may play a critical role in the senescence of SLE BM-MSCs through the p53/p21 pathway.
Related JoVE Video
Ionothermal synthesis of two oxalate-bridged lanthanide(III) chains with slow magnetization relaxation by using a deep eutectic solvent.
Dalton Trans
PUBLISHED: 08-01-2013
Show Abstract
Hide Abstract
Two novel isostructural oxalate-bridged lanthanide(III) chains, (choline)[Ln(ox)(H2O)3Cl]Cl·H2O (Ln = Dy/Er), were first obtained ionothermally by using a choline chloride-oxalic acid eutectic mixture as both solvent and structure-directing agent, both of which show field-induced slow relaxation of magnetization.
Related JoVE Video
Three novel homozygous mutations in the GNPTG gene that cause mucolipidosis type III gamma.
Gene
PUBLISHED: 07-29-2013
Show Abstract
Hide Abstract
Mucolipidosis type III gamma (MLIII gamma) is an autosomal recessive disease caused by a mutation in the GNPTG gene, which encodes the ? subunit of the N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase). This protein plays a key role in the transport of lysosomal hydrolases to the lysosome.
Related JoVE Video
[Cardiac involvement of the type I mucopolysaccharidosis].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 07-17-2013
Show Abstract
Hide Abstract
To investigate the manifestations of cardiac involvement in the patients with mucopolysacharidosis I (MPS I).
Related JoVE Video
Prognostic nutritional index predicts outcomes of malignant pleural mesothelioma.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 06-22-2013
Show Abstract
Hide Abstract
Nutritional status has been associated with long-time outcomes in cancer patients. We investigated whether the prognostic nutritional index (PNI), an indicator of nutritional status, affects overall survival in patients with malignant pleural mesothelioma (MPM).
Related JoVE Video
[Detection of pathogenic mutations in Marfan syndrome by targeted next-generation semiconductor sequencing].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 06-08-2013
Show Abstract
Hide Abstract
To detect pathogenic mutations in Marfan syndrome (MFS) using an Ion Torrent Personal Genome Machine (PGM) and to validate the result of targeted next-generation semiconductor sequencing for the diagnosis of genetic disorders.
Related JoVE Video
Anomalous stability of graphene containing defects covered by a water layer.
Nanoscale
PUBLISHED: 05-23-2013
Show Abstract
Hide Abstract
Defects are inevitably present in graphene and can alter its properties and thus its applications. Interestingly, we find that commonly observed Stone-Wales and double vacancy defects do not affect graphenes hydrophilic and hydrophobic properties and that an adsorbed single water layer does not noticeably affect the defect-containing graphenes electronic properties. Our findings are based on calculations using a density functional tight-binding theory. Specifically, we observe negligible alteration in the interaction strength (less than 0.1 kcal mol(-1)) between a single water layer and graphene upon the incorporation of the various types of defects, which indicates that graphene has relatively stable hydrophilic and hydrophobic properties. The presence of a single water layer causes only negligible changes in the energy gap and a small charge transfer to the aqueous layer (less than 0.1 e). The results indicate that the electronic properties of graphene are determined mainly by its own structural characteristics and are not considerably affected by the adsorbed water layer. Further electronic structure analysis reveals that the two commonly observed defects do not change the sp(2) hybridization characteristics of the C atoms of graphene even in the water environment. Our results are significant for graphene studies and applications in areas such as life sciences and materials science where hydrophilic and hydrophobic properties and electronic properties are important.
Related JoVE Video
Filter properties of chirped fiber Bragg grating Fabry-Perot cavity: a potential wavelength stabilizer of diode laser.
Appl Opt
PUBLISHED: 05-15-2013
Show Abstract
Hide Abstract
We investigate filter properties of chirped fiber Bragg grating (CFBG) (Fabry-Perot) F-P cavity through analyzing the coupled wave equation from one-dimensional Helmholtz equation. We derive an approximate formula of the reflectivity of a CFBG F-P cavity, simulate the central wavelength detuning, and calculate the central wavelength shift with the increase of ambient temperature. In the experiments, we measured the spectra of a diode laser with an FBG/CFBG F-P cavity at 0°C-110°C. The experimental results show that the CFBG F-P cavity can help a diode laser to obtain a less central wavelength shift and a narrower 3 dB reflection bandwidth, compared with the FBG F-P cavity at 0°C-110°C. The research results indicate that the CFBG F-P cavity is a potential wavelength stabilizer of uncooled diode laser.
Related JoVE Video
Complete mitochondrial DNA genome of Pseudobagrus brevicaudatus (Siluriformes: Bagridae).
Mitochondrial DNA
PUBLISHED: 05-08-2013
Show Abstract
Hide Abstract
Abstract The complete mitochondrial genome of Pseudobagrus brevicaudatus (Siluriformes: Bagridae) was sequenced in this study. The total length of the mitogenome is 16,533?bp, with the base composition of 31.6% A, 26.8% T, 15.0%G, 26.6% C. The gene order and genes were the same as that found in other previously reported catfishes, including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding control region. Except for ND6 gene and 8 tRNA genes, all other mitochondrial genes were encoded on the heavy strand. This complete mitogenome data provides the basis for taxonomic and conservation research of this and closely related species.
Related JoVE Video
p53/p21 Pathway involved in mediating cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients.
Clin. Dev. Immunol.
PUBLISHED: 04-30-2013
Show Abstract
Hide Abstract
Our and other groups have found that bone marrow-derived mesenchymal stem cells (BM-MSCs) from systemic lupus erythematosus (SLE) patients exhibited senescent behavior and are involved in the pathogenesis of SLE. Numerous studies have shown that activation of the p53/p21 pathway inhibits the proliferation of BM-MSCs. The aim of this study was to determine whether p53/p21 pathway is involved in regulating the aging of BM-MSCs from SLE patients and the underlying mechanisms. We further confirmed that BM-MSCs from SLE patients showed characteristics of senescence. The expressions of p53 and p21 were significantly increased, whereas levels of Cyclin E, cyclin-dependent kinase-2, and phosphorylation of retinoblastoma protein were decreased in the BM-MSCs from SLE patients and knockdown of p21 expression reversed the senescent features of BM-MSCs from SLE patients. Our results demonstrated that p53/p21 pathway played an important role in the senescence process of BM-MSCs from SLE.
Related JoVE Video
Complete mitochondrial DNA genome of Pseudobagrus truncatus (Siluriformes: Bagridae).
Mitochondrial DNA
PUBLISHED: 04-30-2013
Show Abstract
Hide Abstract
Abstract In this study, the complete mitochondrial DNA (mtDNA) sequence of Pseudobagrus truncatus (Siluriformes: Bagridae) was determined. The complete mtDNA genome sequence of P. truncatus is 16,533 bp in size. It consists of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and one non-coding control region. The gene order and genes were the same as that found in other previously reported catfishes. The overall-based composition was 31.6% A, 26.7% T, 14.9% G and 26.8% C, with a high A?+?T content (58.3%). This complete mitogenome of P. truncatus provides a basic data for studies on species identification, molecular systematics and conservation genetics.
Related JoVE Video
The development of a normalization method for comparing nerve regeneration effectiveness among different graft types.
J. Peripher. Nerv. Syst.
PUBLISHED: 04-29-2013
Show Abstract
Hide Abstract
The inability to compare directly different nerve grafts has been a significant factor hindering the advance of nerve graft development. Due to the abundance of variables that exist in nerve graft construction and multiple assessment types, there has been limited success in comparing nerve graft effectiveness among experiments. Using mathematical techniques on nerve conduction velocity (NCV) autograft data, a normalization function was empirically derived that normalizes differences in gap lengths. Further analysis allowed for the development of the Relative Regeneration Ratio (RRR). The RRR function allows researchers to directly compare nerve graft results based on the NCV data from their respective studies as long as the data was collected at the same post-operation time. This function also allows for comparisons between grafts tested at different gap lengths. Initial testing of this RRR function provided confidence that the function is accurate for a continuum of gap lengths and different nerve graft types.
Related JoVE Video
Replication and fine mapping of asthma-associated loci in individuals of African ancestry.
Hum. Genet.
PUBLISHED: 04-15-2013
Show Abstract
Hide Abstract
Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.
Related JoVE Video
Gonadogenesis and expression pattern of the vasa gene in the sea cucumber Apostichopus japonicus during early development.
Mol. Reprod. Dev.
PUBLISHED: 03-29-2013
Show Abstract
Hide Abstract
Vasa has been extensively used as a germ-line marker to trace the origin and migration pathway of primordial germ cells (PGCs) in many organisms, but little work has been reported on vasa genes and the origin of PGCs in holothurians. Using in situ hybridization and immunohistochemistry, vasa mRNA and protein of the sea cucumber Apostichopus japonicus (Aj-vasa) was detected in the cytoplasm of the unfertilized egg and was equally distributed in the cytoplasm of early embryos, from the two-cell embryo to the blastula, indicating that Aj-vasa mRNA is maternally supplied. Later, expression of both Aj-vasa mRNA and protein centralizes gradually in newly organized structures from blastula to five-tentacle larva, and then is restricted to PGC-like cells of the original gonad in juveniles with 0.1-cm body length. The structure of the gonad develops further from a simple tubular gonad in 0.5-cm-length juveniles to a branched gonad in 3-cm-length juveniles. Our findings showed that the maternal supply of the vasa gene products in A. japonicus is different from that in sea urchin Strongylocentrotus purpuratus, of echinoderm, and suggested that the specialization of PGCs is an epigenesis mechanism in A. japonicus.
Related JoVE Video
Vitellogenin receptor mutation leads to the oogenesis mutant phenotype "scanty vitellin" of the silkworm, Bombyx mori.
J. Biol. Chem.
PUBLISHED: 03-20-2013
Show Abstract
Hide Abstract
The vitellogenin receptor (VgR) mediates the uptake of vitellogenin (Vg) from the hemolymph by developing oocytes.
Related JoVE Video
Expansion of ruminant-specific microRNAs shapes target gene expression divergence between ruminant and non-ruminant species.
BMC Genomics
PUBLISHED: 03-19-2013
Show Abstract
Hide Abstract
Understanding how species-specific microRNAs (miRNAs) contribute to species-specific phenotypes is a central topic in biology. This study aimed to elucidate the role of ruminant-specific miRNAs in shaping mRNA expression divergence between ruminant and non-ruminant species.
Related JoVE Video
A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Keri L Monda, Gary K Chen, Kira C Taylor, Cameron Palmer, Todd L Edwards, Leslie A Lange, Maggie C Y Ng, Adebowale A Adeyemo, Matthew A Allison, Lawrence F Bielak, Guanjie Chen, Mariaelisa Graff, Marguerite R Irvin, Suhn K Rhie, Guo Li, Yongmei Liu, Youfang Liu, Yingchang Lu, Michael A Nalls, Yan V Sun, Mary K Wojczynski, Lisa R Yanek, Melinda C Aldrich, Adeyinka Ademola, Christopher I Amos, Elisa V Bandera, Cathryn H Bock, Angela Britton, Ulrich Broeckel, Quiyin Cai, Neil E Caporaso, Chris S Carlson, John Carpten, Graham Casey, Wei-Min Chen, Fang Chen, Yii-Der I Chen, Charleston W K Chiang, Gerhard A Coetzee, Ellen Demerath, Sandra L Deming-Halverson, Ryan W Driver, Patricia Dubbert, Mary F Feitosa, Ye Feng, Barry I Freedman, Elizabeth M Gillanders, Omri Gottesman, Xiuqing Guo, Talin Haritunians, Tamara Harris, Curtis C Harris, Anselm J M Hennis, Dena G Hernandez, Lorna H McNeill, Timothy D Howard, Barbara V Howard, Virginia J Howard, Karen C Johnson, Sun J Kang, Brendan J Keating, Suzanne Kolb, Lewis H Kuller, Abdullah Kutlar, Carl D Langefeld, Guillaume Lettre, Kurt Lohman, Vaneet Lotay, Helen Lyon, JoAnn E Manson, William Maixner, Yan A Meng, Kristine R Monroe, Imran Morhason-Bello, Adam B Murphy, Josyf C Mychaleckyj, Rajiv Nadukuru, Katherine L Nathanson, Uma Nayak, Amidou N'Diaye, Barbara Nemesure, Suh-Yuh Wu, M Cristina Leske, Christine Neslund-Dudas, Marian Neuhouser, Sarah Nyante, Heather Ochs-Balcom, Adesola Ogunniyi, Temidayo O Ogundiran, Oladosu Ojengbede, Olufunmilayo I Olopade, Julie R Palmer, Edward A Ruiz-Narváez, Nicholette D Palmer, Michael F Press, Evandine Rampersaud, Laura J Rasmussen-Torvik, Jorge L Rodriguez-Gil, Babatunde Salako, Eric E Schadt, Ann G Schwartz, Daniel A Shriner, David Siscovick, Shad B Smith, Sylvia Wassertheil-Smoller, Elizabeth K Speliotes, Margaret R Spitz, Lara Sucheston, Herman Taylor, Bamidele O Tayo, Margaret A Tucker, David J Van Den Berg, Digna R Velez Edwards, Zhaoming Wang, John K Wiencke, Thomas W Winkler, John S Witte, Margaret Wrensch, Xifeng Wu, James J Yang, Albert M Levin, Taylor R Young, Neil A Zakai, Mary Cushman, Krista A Zanetti, Jing Hua Zhao, Wei Zhao, Yonglan Zheng, Jie Zhou, Regina G Ziegler, Joseph M Zmuda, Jyotika K Fernandes, Gary S Gilkeson, Diane L Kamen, Kelly J Hunt, Ida J Spruill, Christine B Ambrosone, Stefan Ambs, Donna K Arnett, Larry Atwood, Diane M Becker, Sonja I Berndt, Leslie Bernstein, William J Blot, Ingrid B Borecki, Erwin P Bottinger, Donald W Bowden, Gregory Burke, Stephen J Chanock, Richard S Cooper, Jingzhong Ding, David Duggan, Michele K Evans, Caroline Fox, W Timothy Garvey, Jonathan P Bradfield, Hakon Hakonarson, Struan F A Grant, Ann Hsing, Lisa Chu, Jennifer J Hu, Dezheng Huo, Sue A Ingles, Esther M John, Joanne M Jordan, Edmond K Kabagambe, Sharon L R Kardia, Rick A Kittles, Phyllis J Goodman, Eric A Klein, Laurence N Kolonel, Loic Le Marchand, Simin Liu, Barbara McKnight, Robert C Millikan, Thomas H Mosley, Badri Padhukasahasram, L Keoki Williams, Sanjay R Patel, Ulrike Peters, Curtis A Pettaway, Patricia A Peyser, Bruce M Psaty, Susan Redline, Charles N Rotimi, Benjamin A Rybicki, Michèle M Sale, Pamela J Schreiner, Lisa B Signorello, Andrew B Singleton, Janet L Stanford, Sara S Strom, Michael J Thun, Mara Vitolins, Wei Zheng, Jason H Moore, Scott M Williams, Shamika Ketkar, Xiaofeng Zhu, Alan B Zonderman, , Charles Kooperberg, George J Papanicolaou, Brian E Henderson, Alex P Reiner, Joel N Hirschhorn, Ruth J F Loos, Kari E North, Christopher A Haiman.
Nat. Genet.
PUBLISHED: 03-18-2013
Show Abstract
Hide Abstract
Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.
Related JoVE Video
Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.
Hum. Mol. Genet.
PUBLISHED: 02-26-2013
Show Abstract
Hide Abstract
Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ~16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E-13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E - 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.
Related JoVE Video
Flavonoids from the cocoon of Rondotia menciana.
Phytochemistry
PUBLISHED: 02-23-2013
Show Abstract
Hide Abstract
Two flavonol glycosides along with four known flavonoids were isolated from the cocoon of the mulberry white caterpillar, Rondotia menciana (Lepidoptera: Bombycidae: Bombycinae), a closely related species of the domesticated silkworm Bombyx mori, both of which feed on leaves of mulberry (Morus alba). The two glycosides were characterized as quercetin 3-O-?-d-galactopyranosyl-(1?3)-?-d-galactopyranoside and kaempferol 3-O-?-d-galactopyranosyl-(1?3)-?-d-galactopyranoside, based on spectroscopic data and chemical evidence. The flavonol galactosides found in the cocoon were not present in the host plant, nor in the cocoon of the silkworm, B. mori. Notably, flavonol glucosides, which are the main constituents of cocoon flavonoids in B. mori mori, were not found in the R. menciana cocoon. The present result strongly suggests that R. menciana is quite unique in that they predominantly use an UDP-galactosyltransferase for conjugation of dietary flavonoids, whereas UDP-glucosyltransferases are generally used for conjugation of plant phenolics and xenobiotics in other insects.
Related JoVE Video
Effects of unfractionated heparin on renal osteodystrophy and vascular calcification in chronic kidney disease rats.
Bone
PUBLISHED: 02-21-2013
Show Abstract
Hide Abstract
Unfractionated heparin (UFH) is the most widely used anticoagulant in hemodialysis for chronic kidney disease (CKD) patients. Many studies have verified that UFH can induce bone loss in subjects with normal bone, but few have focused on its effect on renal osteodystrophy. We therefore investigated this issue in adenine-induced CKD rats. As CKD also impairs mineral metabolism systemically, we also studied the impacts of UFH on serum markers of CKD-mineral and bone disorder (CKD-MBD) and vascular calcification. We administered low and high doses of UFH (1U/g and 2U/g body weight, respectively) to CKD rats and compared them with CKD controls. At sacrifice, the serum markers of CKD-MBD did not significantly differ among the two UFH CKD groups and the CKD control group. The mean bone mineral densities (BMDs) of the total femur and a region of interest (ROI) constituted of trabecular and cortical bone were lower in the high-dose UFH (H-UFH) CKD group than in the CKD control group (P<0.05 and P<0.01, respectively). The BMD of the femoral ROI constituted of cortical bone did not differ between the H-UFH CKD group and the CKD control group. Histomorphometrical changes in the CKD rats indicated secondary hyperparathyroidism, and the femoral trabecular bone volume, but not cortical bone volume, significantly decreased with increasing UFH dose. The same decreasing trend was found in osteoblast parameters, and an increasing trend was found in osteoclast parameters; however, most differences were not significant. Moreover, no distinct statistical differences were found in the comparison of vascular calcium or phosphorus content among the CKD control group and the two UFH CKD groups. Therefore, we concluded that UFH could induce bone loss in CKD rats with secondary hyperparathyroidism, mainly by reducing the trabecular volume and had little effect on cortical bone volume. The underlying mechanism might involve inhibition of osteoblast activity and promotion of osteoclast activity by UFH. We did not find any effect of UFH on vascular calcification in CKD rats with secondary hyperparathyroidism.
Related JoVE Video
Serotonin inhibits apoptosis of pulmonary artery smooth muscle cell by pERK1/2 and PDK through 5-HT1B receptors and 5-HT transporters.
Cardiovasc. Pathol.
PUBLISHED: 02-17-2013
Show Abstract
Hide Abstract
Decreased apoptosis of pulmonary artery smooth muscle cells (PASMCs) plays a key role in pulmonary vascular remodeling in pulmonary hypertension (PH). However, the cause and mechanism of this decrease in apoptosis are still unclear. Serotonin (5-HT) has been shown to be involved in PH by inducing PASMC proliferation through the activation of 5-HT1B receptors (5-HT1BR) and 5-HT transporter (5-HTT). 5-HT1BR and 5-HTT are also involved in abnormal apoptosis in many other pathological processes. Therefore, we hypothesized that 5-HT induces decreases in PASMC apoptosis through 5-HT1BR and 5-HTT.
Related JoVE Video

What is Visualize?

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

How does it work?

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

Video X seems to be unrelated to Abstract Y...

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.