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Find video protocols related to scientific articles indexed in Pubmed.
Serum 25-hydroxyvitamin D levels and lung function in adults with asthma: the HUNT Study.
Eur. Respir. J.
PUBLISHED: 11-15-2014
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The association between vitamin D status and lung function in adults with asthma remains unclear. We studied this cross-sectional association and possible modification by sex and allergic rhinitis in 760 adults (aged 19-55 years) with self-reported asthma in the Nord-Trøndelag Health Study. Serum 25-hydroxyvitamin D (25(OH)D) level <50 nmol·L(-1) was considered deficient. Lung function measurements included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % predicted and FEV1/FVC ratio. Multiple linear regression models were used to estimate adjusted regression coefficients (?) and 95% confidence intervals. 44% of asthma adults had serum 25(OH)D levels <50 nmol·L(-1). Its associations with lung function measures seemed to be modified by sex and allergic rhinitis (p<0.03 for three-way interaction term). Overall, a serum 25(OH)D level <50 nmol·L(-1) was not associated with lung function measurements in subjects with allergic rhinitis in this asthma cohort. In men with asthma but without allergic rhinitis, however, a serum 25(OH)D level <50 nmol·L(-1) was significantly associated with lower FEV1/FVC ratio (? = -8.60%; 95% CI: -16.95%- -0.25%). Low serum 25(OH)D level was not associated with airway obstruction in most asthma adults with the exception of men with asthma but without allergic rhinitis.
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[Pathological characteristics and prognosis of 664 patients with epithelial ovarian cancer: a retrospective analysis].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-25-2014
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To analyze clinicopathologic features and risk factors associated with the recurrence and prognosis of epithelial ovarian cancer (EOC).
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Total synthesis and determination of the absolute configuration of rakicidin a.
J. Am. Chem. Soc.
PUBLISHED: 10-24-2014
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Rakicidin A is a cyclic depsipeptide that has exhibited unique growth inhibitory activity against chronic myelogenous leukemia stem cells. Furthermore, rakicidin A has five chiral centers with unknown stereochemical assignment, and thus, can be represented by one of 32 possible stereoisomers. To predict the most probable stereochemistry of rakicidin A, calculations and structural comparison with natural cyclic depsipeptides were applied. A total synthesis of the proposed structure was subsequently completed and highlighted by the creation of a sterically hindered ester bond (C1-C15) through trans-acylation from an easily established isomer (C1-C13). The analytic data of the synthetic target were consistent with that of natural rakicidin A, and then the absolute configuration of rakicidin A was assigned as 2S, 3S, 14S, 15S, 16R. This work suggests strategies for the determination of unknown chiral centers in other cyclic depsipeptides, such as rakicidin B, C, D, BE-43547, and vinylamycin, and facilitates the investigations of rakicidin A as an anticancer stem cell agent.
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Primary Pancreatic Choriocarcinoma Revealed on FDG PET/CT.
Clin Nucl Med
PUBLISHED: 09-23-2014
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Choriocarcinoma is a cancer that usually occurs in the uterus during pregnancy. Extragonadal choriocarcinoma, although very rare, can occur. The diagnostic dilatation and curettage of the uterus in a 28-year-old woman who had vaginal bleeding and elevated human chorionic gonadotrophin level failed to identify any abnormality. FDG PET/CT revealed abnormal activity in the head of the pancreas. Pathological examination after partial pancreatectomy demonstrated primary choriocarcinoma in the pancreas.
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Intrapartum interventions for singleton pregnancies arising from assisted reproductive technologies.
J Obstet Gynaecol Can
PUBLISHED: 09-16-2014
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To assess whether singleton pregnancies conceived by assisted reproductive technology (ART) are associated with an increased use of intrapartum interventions when compared with spontaneous singleton pregnancies.
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First-principles approach to nonlinear lattice dynamics: anomalous spectra in PbTe.
Phys. Rev. Lett.
PUBLISHED: 09-02-2014
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Here we introduce a new approach to compute the finite temperature lattice dynamics from first principles via the newly developed slave mode expansion. We study PbTe where inelastic neutron scattering reveals strong signatures of nonlinearity as evidenced by anomalous features which emerge in the phonon spectra at finite temperature. Using our slave mode expansion in the classical limit, we compute the vibrational spectra and show remarkable agreement with temperature dependent inelastic neutron scattering measurements. Furthermore, we resolve an experimental controversy by showing that there are no appreciable local nor global spontaneously broken symmetries at finite temperature and that the anomalous spectral features simply arise from two anharmonic interactions. Our approach should be broadly applicable across the periodic table.
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Palmitic Acid-Induced Neuron Cell Cycle G2/M Arrest and Endoplasmic Reticular Stress through Protein Palmitoylation in SH-SY5Y Human Neuroblastoma Cells.
Int J Mol Sci
PUBLISHED: 08-29-2014
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Obesity-related neurodegenerative diseases are associated with elevated saturated fatty acids (SFAs) in the brain. An increase in SFAs, especially palmitic acid (PA), triggers neuron cell apoptosis, causing cognitive function to deteriorate. In the present study, we focused on the specific mechanism by which PA triggers SH-SY5Y neuron cell apoptosis. We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells. Our data further showed that G2/M arrest is involved in elevation of endoplasmic reticular (ER) stress according to an increase in p-eukaryotic translation inhibition factor 2?, an ER stress marker. Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer's disease. Interestingly, SFA-induced ER stress, G2/M arrest and cell apoptosis were reversed by treatment with 2-bromopalmitate, a protein palmitoylation inhibitor. These findings suggest that protein palmitoylation plays a crucial role in SFA-induced neuron cell cycle G2/M arrest, ER stress and apoptosis; this provides a novel strategy for preventing SFA-induced neuron cell dysfunction.
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Development of new population-averaged standard templates for spatial normalization and segmentation of MR images for postnatal piglet brains.
Magn Reson Imaging
PUBLISHED: 08-29-2014
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To design a set of brain templates for postnatal piglet brains based on high-resolution T1-weighted imaging for voxel-based morphometric analysis.
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[The study of clinical value of transarterial chemical perfusion as second-line therapy for late stage pancreatic cancer].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 08-27-2014
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To discuss arterial infusion chemotherapy as second-line treatment for advanced pancreatic carcinoma salvage after failed vein chemotherapy.
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Efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 08-25-2014
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Vascular endothelial growth factor signaling pathway plays a crucial role in angiogenesis and has become a promising target for cancer drug development. We aimed to quantify the overall efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung cancer (NSCLC).
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Lactoferrin Promotes Early Neurodevelopment and Cognition in Postnatal Piglets by Upregulating the BDNF Signaling Pathway and Polysialylation.
Mol. Neurobiol.
PUBLISHED: 08-23-2014
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Lactoferrin (Lf) is a sialic acid (Sia)-rich, iron-binding milk glycoprotein that has multifunctional health benefits. Its potential role in neurodevelopment and cognition remains unknown. To test the hypothesis that Lf may function to improve neurodevelopment and cognition, the diet of postnatal piglets was supplemented with Lf from days 3 to 38. Expression levels of selected genes and their cognate protein profiles were quantitatively determined. The importance of our new findings is that Lf (1) upregulated several canonical signaling pathways associated with neurodevelopment and cognition; (2) influenced ~10 genes involved in the brain-derived neurotrophin factor (BDNF) signaling pathway in the hippocampus and upregulated the expression of polysialic acid, a marker of neuroplasticity, cell migration and differentiation of progenitor cells, and the growth and targeting of axons; (3) upregulated transcriptional and translational levels of BDNF and increased phosphorylation of the cyclic adenosine monophosphate (cAMP) response element-binding protein, CREB, a downstream target of the BDNF signaling pathway, and a protein of crucial importance in neurodevelopment and cognition; and (4) enhanced the cognitive function and learning of piglets when tested in an eight-arm radial maze. The finding that Lf can improve neural development and cognition in postnatal piglets has not been previously described.
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SIRT1-mediated deacetylation of CRABPII regulates cellular retinoic acid signaling and modulates embryonic stem cell differentiation.
Mol. Cell
PUBLISHED: 08-21-2014
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Retinoid homeostasis is critical for normal embryonic development. Both the deficiency and excess of these compounds are associated with congenital malformations. Here we demonstrate that SIRT1, the most conserved mammalian NAD?-dependent protein deacetylase, contributes to homeostatic retinoic acid (RA) signaling and modulates mouse embryonic stem cell (mESC) differentiation in part through deacetylation of cellular retinoic acid binding protein II (CRABPII). We show that RA-mediated acetylation of CRABPII at K102 is essential for its nuclear accumulation and subsequent activation of RA signaling. SIRT1 interacts with and deacetylates CRABPII, regulating its subcellular localization. Consequently, SIRT1 deficiency induces hyperacetylation and nuclear accumulation of CRABPII, enhancing RA signaling and accelerating mESC differentiation in response to RA. Consistently, SIRT1 deficiency is associated with elevated RA signaling and development defects in mice. Our findings reveal a molecular mechanism that regulates RA signaling and highlight the importance of SIRT1 in regulation of ESC pluripotency and embryogenesis.
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Esophageal cancer stem cells express PLGF to increase cancer invasion through MMP9 activation.
Tumour Biol.
PUBLISHED: 08-20-2014
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Cancer stem cells (CSCs) are a distinct population in tumors and cause cancer relapse and metastasis. Thus, treating CSCs are believed to be potential to cure rapidly growing and highly metastatic cancers. To date, CSCs in esophageal cancer have not been characterized. In the current study, we detected significant higher levels of placental growth factor (PLGF) and matrix metalloproteinase 9 (MMP9) in the esophageal cancers with metastasis, compared to those without metastasis, in which the expression levels of PLGF and MMP9 strongly correlated with each other. Thus, we used a human esophageal cancer cell line, TE-1, to examine the cross talk of PLGF and MMP9. We found that the levels of PLGF in TE-1 cells positively affected the levels of MMP9, while the levels of MMP9 did not affected the levels of PLGF, suggesting that PLGF may activate MMP9 in esophageal cancer cells. Then, we separated PLGF-positive and PLGF-negative TE-1 cells that had been transfected with a GFP reporter under a PLGF promoter by flow cytometry. We found that PLGF-positive cells grew significantly faster than PLGF-negative cells both in vitro and in vivo in a stereotactical implantation model, suggesting that PLGF-positive cells are likely CSCs in esophageal cancer. Taken together, we demonstrate that PLGF-positive cells appear to be CSCs in esophageal cancer, and they may release PLGF to promote cancer metastasis through MMP9 activation.
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Total syntheses of parthenolide and its analogues with macrocyclic stereocontrol.
J. Med. Chem.
PUBLISHED: 08-20-2014
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The first total synthesis of parthenolide (1) is described. The key feature of this synthesis is the formation of a 10-membered carbocylic ring by a macrocyclic stereocontrolled Barbier reaction, followed by a photoinduced Z/E isomerization. The biological evaluation of a small library of parthenolide analogues (19, 33, and 34) disclosed a preliminary structure-activity relationship (SAR). The results revealed that the C1, C10 double bond configuration of parthenolide has little or no effect on the activity, and the C6 and C7 configurations of the lactone ring have a moderate impact on the activities against some cancer cell lines.
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Analysis of bacterial pathogens causing acute diarrhea on the basis of sentinel surveillance in Shanghai, China, 2006-2011.
Jpn. J. Infect. Dis.
PUBLISHED: 07-25-2014
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Acute diarrhea is the most common infectious disease worldwide and its causes vary from one region to another. We aimed to analyze the spectrum and epidemiological characteristics of pathogens from 22,386 outpatients with acute diarrhea on the basis of surveillance data from Shanghai, China, during 2006-2011. The following 8 pathogens were isolated and identified using standard methods: Salmonella, Shigella, Vibrio cholerae, V. parahaemolyticus, enteropathogenic Escherichia coli, enterotoxigenic E. coli, enteroinvasive E. coli, and enterohemorrhagic E. coli. In total, 2,234 strains of pathogens were obtained and the overall isolation rate of these 8 pathogens gradually decreased from 17.1% in 2006 to 7.4% in 2011. V. parahaemolyticus was the most frequently identified pathogen, followed by Shigella and Salmonella. The isolation rate of V. parahaemolyticus notably varied by season, whereas Salmonella and Shigella infections showed little seasonal variation. Age-related variation was also observed. V. parahaemolyticus infection occurred more often in patients aged 20-40 years. S. enterica serovar Enteritidis and S. flexneri were the most common serotypes of Salmonella and Shigella, respectively. The descending trend observed in the isolation rate of pathogens from the current surveillance suggests an urgent requirement or improvement.
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L-3-n-butylphthalide improves cognitive impairment of APP/PS1 mice by BDNF/TrkB/PI3K/AKT pathway.
Int J Clin Exp Med
PUBLISHED: 07-15-2014
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L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia and amyloid-beta (Abeta)-induced animal models by inhibiting oxidative injury, neuronal apoptosis and glial activation, regulating amyloid-beta protein precursor (AbetaPP) processing and reducing Abeta generation. The objective of this study was to investigate the effects of L-3-n-butylphthalide on memory impairment and the expression of brain neurotrophic derived factor (BNDF), kinaseB (TrkB), phosphatidylinositol 3 kinase (PI3K) and Akt in APP/PS1 double transgenic mouse models. APP/PS1 double transgenic mice were administered 30 mg/kg•d L-NBP and 10 mg/kg•d L-NBP for one month. The learning and memory ability were studied using the water maze test. Protein expression and transcript levels of genes in the mice hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. The results demonstrated that both 30 mg/kg•d L-NBP and 10 mg/kg•d L-NBP doses of L-NBP significantly increased memory capability and the expression of hippocampal BDNF/TrkB/PI3K/AKT in mice The results suggested that L-NBP treatment may reverse memory impairment in APP/PS1 transgenic mice, and BDNF/TrkB/PI3K/AKT, may be involved in this process.
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Heterogeneous associations of insoluble dietary fibre intake with subsequent glycosylated Hb levels among Chinese adults with type 2 diabetes: a quantile regression approach.
Br. J. Nutr.
PUBLISHED: 07-09-2014
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Dietary fibre intake has been suggested to reduce blood glucose levels in diabetic patients, particularly when glycosylated Hb (HbA1c) levels are high. In the present study, we used a quantile regression (QR) approach to characterise the possible heterogeneous associations of dietary fibre intake with HbA1c levels in Chinese diabetic patients. A total of 497 diabetic patients participated in the baseline survey in 2006 and in the follow-up survey in 2011, both of which were conducted in Pudong New Area of Shanghai, China. Structured in-person interviews were conducted to collect information on demographic characteristics and lifestyle factors. Dietary intake was assessed using a validated FFQ. Blood samples were collected during the interviews for biochemical assays. QR models were used to examine the heterogeneous associations of dietary factors with HbA1c levels. A significant marginal association of insoluble dietary fibre intake with subsequent HbA1c levels was observed only when the HbA1c level was over 6·8%. The associations appeared to be greater when the quantile levels of HbA1c were higher. The coefficient estimates were -0·174 (95% CI -0·433, -0·025) at the quantile of 0·60, -0·200 (95% CI -0·306, -0·008) at 0·70, -0·221 (95% CI -0·426, -0·117) at 0·80, and -0·389 (95% CI -0·516, -0·018) at 0·90. A similar pattern was observed for the associations of dietary glycaemic index (GI) value with HbA1c levels. In conclusion, the present results indicate that the associations of insoluble dietary fibre intake and GI value with subsequent HbA1c levels depend on glycaemic control status in Chinese diabetic patients. More studies are required to confirm our findings.
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Primary squamous cell carcinoma of the thyroid on FDG PET/CT.
Clin Nucl Med
PUBLISHED: 07-08-2014
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Primary squamous cell carcinoma of the thyroid is rare. We present FDG PET/CT findings on 2 male patients with primary squamous cell carcinoma of the thyroid. Elevated FDG activity was visualized on primary thyroid tumor and metastatic lesions on both patients.
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[Risk factors associated with lymph node metastasis and prognosis in 69 patients with rectal neuroendocrine tumors].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 06-24-2014
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To investigate risk factors associated with lymph node metastasis and prognosis of rectal neuroendocrine tumor(NET).
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Spiral-structured fiber Bragg grating for contact force sensing through direct power measurement.
Opt Express
PUBLISHED: 06-13-2014
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A high-sensitivity fiber Bragg grating (FBG) force sensor based on direct optical power measurement is presented. The approach utilizes a novel structure where the FBG is mounted on a thin tube-like fixture spirally. Contact force measurement is achieved through direct measurement of the FBG reflection power at a single wavelength using a power meter. The measuring system in our approach is simple and does not require processing of massive amount of spectral data, enabling real-time contact force monitoring. When force is applied to the FBG sensor, the unique spiral structure leads to FBG chirping and reflection spectrum broadening. A proportional relationship and linear fit are found between the force applied (up to 1.55 N) and the optical power reflected by the proposed FBG sensor. An average sensitivity of 11.16 dB/N is experimentally achieved. This design significantly reduces system complexity and improves data processing speed, which has great practical value in real-time FBG sensing applications.
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Objective tongue inspection on 142 liver cancer patients with damp-heat syndrome.
Chin J Integr Med
PUBLISHED: 06-10-2014
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To establish the diagnosis evidence of objective tongue inspection for liver cancer (LC) patients with damp-heat syndrome (DHS) by dynamically observing their tongue figures using modern tongue image analytic apparatus, and to explore the effect of intervention on the tongue figures.
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Intense FDG activity in focal hepatic steatosis.
Clin Nucl Med
PUBLISHED: 05-31-2014
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A 38-year-old woman underwent PET/CT to evaluate possible hepatic malignancy. The images revealed intense FDG activity in several hypodense regions in the liver, most prominent in the lateral segment of the left lobe. The pathological examination showed that the patient had focal hepatic steatosis.
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Disordered hepcidin-ferroportin signaling promotes breast cancer growth.
Cell. Signal.
PUBLISHED: 05-24-2014
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Iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including cancers. Burgeoning evidence indicates that the central signaling of iron homeostasis, the hepcidin-ferroportin axis, is misregulated in cancers. Nonetheless, the mechanisms of misregulated expression of iron-related genes along this signaling in cancers remain largely unknown. In the current study, we found increased levels of serum hepcidin in breast cancer patients. Reduction of hepatic hepcidin through administration of heparin restrained tumorigenic properties of breast tumor cells. Mechanistic investigation revealed that increased iron, bone morphogenetic protein-6 (BMP6) and interleukin-6 (IL-6) jointly promoted the synthesis of hepatic hepcidin. Tumor hepcidin expression was marginally increased in breast tumors relative to adjacent tissues. In contrast, tumor ferroportin concentration was greatly reduced in breast tumors, especially in malignant tumors, compared to adjacent tissues. Elevation of ferroportin concentration inhibited cell proliferation in vitro and in vivo by knocking down tumor hepcidin expression. Additionally, increased IL-6 was demonstrated to jointly enhance the tumorigenic effects of iron through enforcing cell growth. Our combined data overall deciphered the machinery that altered the hepcidin-ferroportin signaling in breast cancers. Thus, targeting the hepcidin-ferroportin signaling would represent a promising therapeutics to restrain breast cancer growth.
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Thermosensitive hydrogel used in dual drug delivery system with paclitaxel-loaded micelles for in situ treatment of lung cancer.
Colloids Surf B Biointerfaces
PUBLISHED: 05-24-2014
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In this study, an in situ gel-based dual drug delivery system (PEG-PCL-PEG/DDP+MPEG-PCL/PTX, abbreviated as PDMP) was prepared through the combination of a cisplatin (DDP)-containing thermosensitive hydrogel (PEG-PCL-PEG/DDP, PECE/DDP) and paclitaxel (PTX)-loaded polymeric micelles (average diameter of 20.1nm). PDMP is a free-flowing solution at room temperature and forms a stationary gel at body temperature, allowing it to serve as a drug depot for the in situ treatment of lung cancer. For in vivo experiments, the xenografted lung cancer model was used to evaluate the anti-tumor efficacy of the PDMP. The results suggested that PDMP is effective at inhibiting tumor growth and prolonging the survival time of tumor-bearing BALB/c nude mice. The survival time of the PDMP-treated group (53 days) is significantly higher than that of other groups (40 days from the free DDP+PTX group, 26 days from the blank PECE group, 25 days from the normal saline group, p<0.05). Immunohistochemical analysis revealed that tumors in the PDMP group had fewer microvessels and lower proliferation activity compared with those of the control group. Thus, PDMP may have great potential for in situ treatment of lung cancer by minimally invasive injection methods.
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Small molecule metabolite biomarker candidates in urine from mice exposed to formaldehyde.
Int J Mol Sci
PUBLISHED: 05-21-2014
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Formaldehyde (FA) is a ubiquitous compound used in a wide variety of industries, and is also a major indoor pollutant emitted from building materials, furniture, etc. Because FA is rapidly metabolized and endogenous to many materials, specific biomarkers for exposure have not been identified. In this study, we identified small metabolite biomarkers in urine that might be related FA exposure. Mice were allowed to inhale FA (0, 4, 8 mg/m3) 6 h per day for 7 consecutive days, and urine samples were collected on the 7th day of exposure. Liquid chromatography coupled with time of flight-mass spectrometry and principal component analysis (PCA) was applied to determine alterations of endogenous metabolites in urine. Additionally, immune toxicity studies were conducted to ensure that any resultant toxic effects could be attributed to inhalation of FA. The results showed a significant decrease in the relative rates of T lymphocyte production in the spleen and thymus of mice exposed to FA. Additionally, decreased superoxide dismutase activity and increased reactive oxygen species levels were found in the isolated spleen cells of exposed mice. A total of 12 small molecules were found to be altered in the urine, and PCA analysis showed that urine from the control and FA exposed groups could be distinguished from each other based on the altered molecules. Hippuric acid and cinnamoylglycine were identified in urine using exact mass and fragment ions. Our results suggest that the pattern of metabolites found in urine is significantly changed following FA inhalation, and hippuric acid and cinnamoylglycine might represent potential biomarker candidates for FA exposure.
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Nanosilver incurs an adaptive shunt of energy metabolism mode to glycolysis in tumor and nontumor cells.
ACS Nano
PUBLISHED: 05-12-2014
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Due to its significant antimicrobial properties, nanosilver (nAg) has been substantially used in a wide spectrum of areas. This has raised the concerns on the detrimental effects on environment and human health. Although numerous studies have documented nAg-mediated toxicity to cells or organisms, little attempt has been made to study the biological impacts of nAg on cells at nontoxic concentrations, namely, the distinct biological effects that can be separated from direct cytotoxicity. Here, we studied nAg-mediated effects on energy metabolism in cells under sublethal exposure. Treatment of nAg at nontoxic concentrations resulted in a decline of ATP synthesis and attenuation of respiratory chain function in nontumor HEK293T cells and tumor cells with differential respiration rate, including HepG2, HeLa, A498, and PC3 cells. Cellular energy homeostasis was switched from oxidative phosphorylation-based aerobic metabolism to anaerobic glycolysis, which is an adaption process to satisfy the energy demand for cell survival. Nanospheres with smaller size showed greater capability to alter cellular energy metabolism than those with larger size or nanoplates. Mechanistic investigation manifested that inhibition of PGC-1? by nAg was, at least partially, accountable for the transition from oxidative phosphorylation to glycolysis. Additionally, altered expression of a few energy metabolism-related genes (such as PFKFB3 and PDHA1) was also involved in the transition process. We further showed nAg-induced depolarization of mitochondrial membrane potential and reduction of respiratory chain complex activity. Together, our combined results uncovered the mechanisms by which nAg induced energy metabolism reprogramming in both tumor and nontumor cells under sublethal dosage.
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Widespread gouty tophi on 18F-FDG PET/CT imaging.
Clin Nucl Med
PUBLISHED: 05-09-2014
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A 72-year-old man was admitted to our hospital because of worsening polyarticular swelling pain. An F-FDG PET/CT was performed to evaluate the extent of a suspected gouty attack and to exclude any unexpected malignancy. The images showed multiple juxta-articular and subcutaneous foci of elevated F-FDG activity in both upper and lower extremities, including the hands, elbows, shoulders, hips, knees, ankles, and feet. Diagnosis of an acute, severe gouty attack was eventually made. The patient responded well to antigouty therapy.
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Antitumor efficacy of DMSA modified Fe3O4 magnetic nanoparticles combined with arsenic trioxide and adriamycin in Raji cells.
J Biomed Nanotechnol
PUBLISHED: 04-18-2014
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The objective of the present study was to investigate the anticancer efficacy of dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles (MNPs) combined with arsenic trioxide (As2O3) and doxorubicin (ADM) in non-Hodgkin's lymphoma (NHL) cell line (Raji cells). The growth inhibition rate of Raji cells was determined by MTT assay. Characteristics of DMSA-Fe3O4 MNPs and distribution of nanoparticles taken up by Raji cells were observed under a transmission electron microscopy (TEM). Further, apoptosis of cells and intracellular concentration of ADM were detected by flow cytometry (FCM). DAPI staining was used to view apoptotic cellular morphology. Subsequently, transcription and protein expression levels of bcl-2, NFKB, survivin, bax, p53 and caspase-3 were determined by reverse transciptase polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. The results of MTT assay indicated that the inhibition of Raji cells by the combined form of ADM and As2O3 was significantly higher than either ADM or As2O3 alone. However, ADM-As2O3 MNPs proved superior over all other groups. TEM observation revealed that the majority of MNPs were quasi-spherical with an average diameter of about 18 nm and the MNPs taken up by cells were located in the endosome vesicles of cytoplasm. The apoptotic rate and accumulation of intracellular ADM in ADM-As2O3 MNPs group were significantly higher than those in control, ADM, As2O3 and ADM+As2O3, groups. In addition, DAPI staining of Raji cells from ADM-As,O3 MNPs group clearly exhibited more morphological changes (severe structural alterations) than other groups. Moreover, transcription and protein expression of bcl-2, NFKB, survivin, bax, p53 and caspase-3 of Raji cells were regulated at the most remarkable extent in ADM-As2O3, MNPs group as compared with other groups. These findings suggest that the antitumor efficacy of the combination of novel ADM-As2O3, MNPs on Raji cells would be a promising strategy for lymphoma therapy.
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Characterization of regulatory regions involved in the inducible expression of chiB in Bacillus thuringiensis.
Arch. Microbiol.
PUBLISHED: 03-26-2014
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Expression of the chiB gene from Bacillus thuringiensis Bti75 was defined as inducible by the use of transcriptional fusions with the bgaB reporter gene. The transcription start site of the chiB gene was identified as the C base located 132 base pairs upstream of the start codon. Analysis of 5' and 3' deletions of the chiB promoter region revealed that the sequence from position -192 to +36 with respect to the transcription start site was necessary for wild-type levels of inducible expression of the chiB gene. The minimal promoter region for the expression of chiB gene was identified as the sequence from position -100 to +12. Furthermore, a 16-bp sequence (designated dre) downstream of the minimal promoter region of chiB was shown to be required for chitin induction. To confirm the function of this 16-bp sequence, 25 base substitutions were introduced into the dre site. Most of the mutations resulted in constitutive expression, or the efficiency of induction decreased. All mutations identified the dre sequence as a critical site for the inducible expression of chiB. In addition, the dre site was shown to interact with a sequence-specific DNA binding factor of strain Bti75 cultured in the absence of the inducer.
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Transgenic 4-1BBL-engineered vaccine stimulates potent Gag-specific therapeutic and long-term immunity via increased priming of CD44(+)CD62L(high) IL-7R(+) CTLs with up- and downregulation of anti- and pro-apoptosis genes.
Cell. Mol. Immunol.
PUBLISHED: 03-25-2014
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Human immunodeficiency virus type-1 (HIV-1)-specific dendritic cell (DC) vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. We previously demonstrated that the HIV-1 Gag-specific Gag-Texo vaccine stimulated Gag-specific effector CD8(+) cytotoxic T lymphocyte (CTL) responses, leading to completely protective, but very limited, therapeutic immunity. In this study, we constructed a recombinant adenoviral vector, adenovirus (AdV)4-1BBL, which expressed mouse 4-1BB ligand (4-1BBL), and generated transgenic 4-1BBL-engineered OVA-Texo/4-1BBL and Gag-Texo/4-1BBL vaccines by transfecting ovalbumin (OVA)-Texo and Gag-Texo cells with AdV4-1BBL, respectively. We demonstrate that the OVA-specific OVA-Texo/4-1BBL vaccine stimulates more efficient OVA-specific CTL responses (3.26%) compared to OVA-Texo-activated responses (1.98%) in wild-type C57BL/6 mice and the control OVA-Texo/Null vaccine without transgenic 4-1BBL expression, leading to enhanced therapeutic immunity against 6-day established OVA-expressing B16 melanoma BL6-10OVA cells. OVA-Texo/4-1BBL-stimulated CTLs, which have a CD44(+)CD62L(high) IL-7R(+) phenotype, are likely memory CTL precursors, demonstrating prolonged survival and enhanced differentiation into memory CTLs with functional recall responses and long-term immunity against BL6-10OVA melanoma. In addition, we demonstrate that OVA-Texo/4-1BBL-stimulated CTLs up- and downregulate the expression of anti-apoptosis (Bcl2l10, Naip1, Nol3, Pak7 and Tnfrsf11b) and pro-apoptosis (Casp12, Trp63 and Trp73) genes, respectively, by RT(2) Profiler PCR array analysis. Importantly, the Gag-specific Gag-Texo/4-1BBL vaccine also stimulates more efficient Gag-specific therapeutic and long-term immunity against HLA-A2/Gag-expressing B16 melanoma BL6-10Gag/A2 cells than the control Gag-Texo/Null vaccine in transgenic HLA-A2 mice. Taken together, our novel Gag-Texo/4-1BBL vaccine, which is capable of stimulating potent Gag-specific therapeutic and long-term immunity, may represent a new immunotherapeutic vaccine for controlling HIV-1 infection.Cellular & Molecular Immunology advance online publication, 8 September 2014; doi:10.1038/cmi.2014.72.
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The use of glyburide in the management of gestational diabetes mellitus: a meta-analysis.
Adv Med Sci
PUBLISHED: 03-22-2014
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Glyburide has been used for managing gestational diabetes mellitus (GDM) in a number of countries. It is rather inexpensive. However, its efficacy and safety remain controversial. With this meta-analysis, we evaluated glyburide in comparison with insulin.
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Evaluating the impact of environmental temperature on global highly pathogenic avian influenza (HPAI) H5N1 outbreaks in domestic poultry.
Int J Environ Res Public Health
PUBLISHED: 03-16-2014
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The emergence and spread of highly pathogenic avian influenza (HPAI) A virus subtype H5N1 in Asia, Europe and Africa has had an enormously socioeconomic impact and presents an important threat to human health because of its efficient animal-to-human transmission. Many factors contribute to the occurrence and transmission of HPAI H5N1 virus, but the role of environmental temperature remains poorly understood. Based on an approach of integrating a Bayesian Cox proportional hazards model and a Besag-York-Mollié (BYM) model, we examined the specific impact of environmental temperature on HPAI H5N1 outbreaks in domestic poultry around the globe during the period from 1 December 2003 to 31 December 2009. The results showed that higher environmental temperature was a significant risk factor for earlier occurrence of HPAI H5N1 outbreaks in domestic poultry, especially for a temperature of 25 °C. Its impact varied with epidemic waves (EWs), and the magnitude of the impact tended to increase over EWs.
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The discovery of potentially selective human neuronal nitric oxide synthase (nNOS) Inhibitors: a combination of pharmacophore modelling, CoMFA, virtual screening and molecular docking studies.
Int J Mol Sci
PUBLISHED: 03-16-2014
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Neuronal nitric oxide synthase (nNOS) plays an important role in neurotransmission and smooth muscle relaxation. Selective inhibition of nNOS over its other isozymes is highly desirable for the treatment of neurodegenerative diseases to avoid undesirable effects. In this study, we present a workflow for the identification and prioritization of compounds as potentially selective human nNOS inhibitors. Three-dimensional pharmacophore models were constructed based on a set of known nNOS inhibitors. The pharmacophore models were evaluated by Pareto surface and CoMFA (Comparative Molecular Field Analysis) analyses. The best pharmacophore model, which included 7 pharmacophore features, was used as a search query in the SPECS database (SPECS®, Delft, The Netherlands). The hit compounds were further filtered by scoring and docking. Ten hits were identified as potential selective nNOS inhibitors.
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MoLys2 is necessary for growth, conidiogenesis, lysine biosynthesis, and pathogenicity in Magnaporthe oryzae.
Fungal Genet. Biol.
PUBLISHED: 03-16-2014
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Amino acid biosyntheses are complex but essential processes in growth and differentiation of eukaryotic cells. In the budding yeast Saccharomyces cerevisiae, the lysine biosynthesis via the ?-aminoadipate (AA) pathway involves several steps, including reduction of AA to AA 6-semialdehyde by AA reductase ScLys2. In filamentous fungus Penicillium chrysogenum, disruption of the LYS2 gene blocked the lysine biosynthesis but promoted the production of the secondary metabolite penicillin. In comparison, little is known about the function of AA reductase Lys2 in phytopathogenic fungi. We here characterized the functions of MoLys2, a homolog of ScLys2, from the rice blast fungus Magnaporthe oryzae. Our results showed that the ?Molys2 mutants were auxotrophic for lysine. The ?Molys2 mutants also exhibited drastic reduction in pathogenicity on rice, inducing small disease lesions. Microscopic examination of the lesions revealed that the invasive hyphae of ?Molys2 mutants were mostly restricted to the primary infected leaf sheath cells. In addition, exogenous lysine restored the production of conidia and near wild-type appressoria differentiation, and rescued the defect of pathogenicity in conidia infection of detached barely and rice leaf sheath. Our results indicated that MoLys2 is necessary for lysine biosynthesis that affects growth, conidiogenesis, and pathogenicity of the fungus. This study does implicate the potential for targeting lysine biosynthesis for the development of novel fungicides against M. oryzae.
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Lactoferrin up-regulates intestinal gene expression of brain-derived neurotrophic factors BDNF, UCHL1 and alkaline phosphatase activity to alleviate early weaning diarrhea in postnatal piglets.
J. Nutr. Biochem.
PUBLISHED: 03-14-2014
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The molecular mechanisms underlying how dietary lactoferrin (Lf) impacts gut development and maturation and protects against early weaning diarrhea are not well understood. In this study, we supplemented postnatal piglets with an Lf at a dose level of 155 and 285 mg/kg/day from 3 to 38 days following birth. Our findings show that the high dose of Lf up-regulated messenger RNA expression levels of genes encoding brain-derived neurotrophic factor (BDNF) and ubiquitin carboxy-terminal hydrolase L1 (ubiquitin thiolesterase (UCHL1) and, to a lesser extent, glial cell line-derived neurotrophic factor, in the duodenum (P<.05). Piglets in the high and low Lf group had 30% and 7% larger jejunal crypts compared with the control group (P<.05). Escherichia coli 16S rRNA copy number per gram of ascending colon contents was significantly reduced (P=.001), while the copy number of Bifidobacteria and Lactobacillus spp. was not affected. In addition, Lf increased intestinal alkaline phosphatase activity (P<.05) and delayed the onset of food transitional diarrhea, reducing its frequency and duration (P<.05). The incidence of diarrhea in the high and low Lf groups was decreased 54% and 15%, respectively, compared with the control group (P=.035). In summary, these findings provide new evidence that dietary Lf supplementation up-regulated gene expression of BDNF and UCHL1, decreased the colon microbiota of E. coli, improved gut maturation and reduced early weaning diarrhea in piglets. The molecular basis underlying these findings suggests that Lf may enhance gut development and immune function by providing new insight into the gut-brain-microbe axis that has not been previously reported.
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Magneto-fluorescent core-shell supernanoparticles.
Nat Commun
PUBLISHED: 03-12-2014
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Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magneto-fluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle 'core', which is fully surrounded by a 'shell' of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.
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An MR-conditional high-torque pneumatic stepper motor for MRI-guided and robot-assisted intervention.
Ann Biomed Eng
PUBLISHED: 03-09-2014
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Magnetic resonance imaging allows for visualizing detailed pathological and morphological changes of soft tissue. MR-conditional actuations have been widely investigated for development of image-guided and robot-assisted surgical devices under the Magnetic resonance imaging (MRI). This paper presents a simple design of MR-conditional stepper motor which can provide precise and high-torque actuation without adversely affecting the MR image quality. This stepper motor consists of two MR-conditional pneumatic cylinders and the corresponding supporting structures. Alternating the pressurized air can drive the motor to rotate each step in 3.6° with the motor coupled to a planetary gearbox. Experimental studies were conducted to validate its dynamics performance. Maximum 800 mN m output torque is achieved. The motor accuracy independently varied by two factors: motor operating speed and step size, was also investigated. The motor was tested within a 3T Siemens MRI scanner (MAGNETOM Skyra, Siemens Medical Solutions, Erlangen, Germany) and a 3T GE MRI scanner (GE SignaHDx, GE Healthcare, Milwaukee, WI, USA). The image artifact and the signal-to-noise ratio (SNR) were evaluated for study of its MRI compliancy. The results show that the presented pneumatic stepper motor generated 2.35% SNR reduction in MR images. No observable artifact was presented besides the motor body itself. The proposed motor test also demonstrates a standard to evaluate the pneumatic motor capability for later incorporation with motorized devices used under MRI.
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Relationship Between Adiposity and Pulmonary Function in School-Aged Canadian Children.
Pediatr Allergy Immunol Pulmonol
PUBLISHED: 02-26-2014
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Reduced lung function has been observed in adults with excess adiposity; however, in children, the relationship between adiposity and lung function is not clearly understood. A sample of 1,583 children, less than 18 years of age, from the Canadian Health Measures Survey (CHMS) was used to examine the associations of various anthropometric and skinfold measures with lung function parameters. The mean age of the sample was 12.15 (0.096). In normal weight boys, body mass index (BMI) was positively associated with forced vital capacity (FVC), FEV0.75 and FEV1; while in overweight or obese boys, waist circumference (WC) and waist-to-hip ratio showed inverse correlations with pulmonary function measures. Similarly, in normal weight girls, BMI and WC had positive associations with lung function measures but no inverse effect of adiposity was observed in overweight or obese girls. Skinfold analysis showed that only triceps skinfold had a significant inverse association with FVC and borderline significant associations with FEV0.75 and FEV1 in normal weight boys; while in overweight or obese boys, all the skinfold indicators displayed inverse correlations with lung function. The best predictor of lung function was triceps skinfold with ?std=-0.3869 for FVC, -0.3496 for FEV0.75 and -0.3668 for FEV1. No inverse correlations between skinfolds and lung function were observed in girls. Adiposity had differing effects on respiratory function that were dependent on sex and BMI group with the most significant effect on the overweight or obese boys. The most important indicator of adiposity in boys with BMI <30?kg/m(2) was triceps skinfold. In girls, adiposity was not associated with poor lung function.
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The CD8 antiviral factor (CAF) can suppress HIV-1 transcription from the long terminal repeat (LTR) promoter in the absence of elements upstream of the CATATAA box.
Virol. J.
PUBLISHED: 02-26-2014
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The CD8 Antiviral Factor (CAF) suppresses viral transcription from the HIV-1 Long Terminal Repeat (LTR) promoter in a non-cytolytic manner. However, the region on the LTR upon which CAF acts is unknown. Our objective was to determine the region on the LTR upon which CAF acts to suppress HIV-1 transcription.
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Exposure to bisphenol A among school children in eastern China: A multicenter cross-sectional study.
J Expo Sci Environ Epidemiol
PUBLISHED: 02-25-2014
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Bisphenol A (BPA) is one of the highest production and consumption volume chemicals in the world. Although exposure of children to BPA has been studied in Western countries, little is known about its level in China. In this study, total BPA was measured in the morning urine samples of 666 school children aged 9-12 years from three regions in eastern China in 2012. A rapid and sensitive ultraperformance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS) method was used for the measurement and urinary concentrations of BPA were presented as unadjusted (ng/ml), creatinine-adjusted (?g/g creatinine) and specific gravity (SG)-adjusted (ng/ml) forms. BPA was detected in 98.9% of urine samples with their unadjusted concentrations ranging from 0.1 to 326.0?ng/ml (LOD=0.06?ng/ml), indicating that the exposure of BPA was common for school children living in eastern China. The geometric mean and median of BPA was 1.11?ng/ml (creatinine-adjusted: 2.32??g/g creatinine; SG-adjusted: 1.17?ng/ml) and 1.00?ng/ml (creatinine-adjusted: 2.22??g/g creatinine; SG-adjusted: 1.07?ng/ml), respectively. The highest urinary BPA level was found in the age group of 12 years with GM concentration of 1.55?ng/ml, and it decreased with decreasing age (11 years: 1.18?ng/ml; 10 years: 1.05?ng/ml; and 9 years: 0.99?ng/ml), but there was a lack of consistency for age associated with BPA levels in three study areas. The estimated daily intake of BPA (0.023??g/kg bw/day) was much lower than the tolerable daily and reference dose of 50??g/kg bw/day recommended by either the European Food Safety Authority or the US Environment Protection Agency. There was no significant difference in urinary BPA concentrations between children who were overweight or obese and those with normal weight (P=0.26), whereas BPA daily intake was unexpectedly higher among normal-weight children (P=0.003). Compared with creatinine correction, the correction method of specific gravity is preferred to evaluate BPA exposure for children.
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Prolonged temporal interaction for peripheral visual processing in schizophrenia: evidence from a three-flash illusion.
Schizophr. Res.
PUBLISHED: 02-25-2014
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Coherent perception of the visual world requires orderly processing of spatially and temporally distributed visual information across the visual field. The organization of this visual information is impaired in schizophrenia. We previously found that visual temporal integration in patients is prolonged, using flashes presented to the central fovea. In this study, we investigated this temporal interaction in both the fovea and fairly far out in the peripheral visual field.
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Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer.
Lab. Invest.
PUBLISHED: 02-13-2014
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Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal (GI) tract associated with an increased risk of colorectal cancer (CRC). Current treatments for both IBD and colitis-associated CRC suffer from numerous side effects. Parthenolide (PTL) is a sesquiterpene lactone with anti-inflammatory activity, and previous studies have demonstrated that PTL is a potent inhibitor of the NF-?B pathway. Micheliolide (MCL), substantially more stable than PTL in vivo, was recently developed, and this study aimed to decipher its suitability as therapeutic tool for IBD and IBD-associated diseases. Similar to PTL, MCL inhibited NF-?B activation and subsequent pro-inflammatory pathways activation in vitro. Pro-drug forms of both compounds inhibited the DSS-induced colitis when administrated intraperitoneally or encapsulated in a polysaccharide gel designed to release drugs in the colon. Interestingly, MCL was found to attenuate carcinogenesis in AOM/DSS-induced CRC, thus providing new candidate for the treatment of inflammatory bowel disease and CRC.
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Diagnostic value of automated 3D ultrasound for incisional hernia.
Ultrasound Med Biol
PUBLISHED: 02-13-2014
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The automated volume scanning system (AVSS) has been applied in breast diseases, but its use in incisional hernias has not been reported. In this study, conventional handheld B-mode ultrasound (HHUS) and AVSS examined a total of 122 hernia defects in 78 patients. The results from two modalities were then compared with surgical findings for the purpose of assessing the diagnostic value of AVSS. Statistics showed that surgeries identified 38 small, 23 medium and 17 large incisional hernias. The results of AVSS completely agreed with surgical findings; however, HHUS misidentified nine large hernias as medium and seven medium hernias as large. AVSS proved to be more accurate than HHUS in measuring the length and width of the hernia. It also outperformed HHUS in both detecting the incisional hernias (91.8% vs. 78.7%, p = 0.00) and determining hernia contents (89.3% vs. 68.0%, p = 0.00). Moreover, the coronal images AVSS obtained clearly displayed the shapes of the hernias, with 46 being regular and 32 irregular. Overall, AVSS can be used as a promising diagnostic modality for incisional hernias.
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Transmission and evolution of hepatitis C virus in HCV seroconverters in HIV infected subjects.
Virology
PUBLISHED: 01-15-2014
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HIV/HCV co-infection provides a model to determine the role of immunity on HCV transmission and evolution. In this study HCV transmission and evolution were evaluated in 6 HCV seroconverters in HIV-infected subjects with a wide range of CD4 cell count. The HCV envelope E1/E2 sequences were analyzed for transmission bottleneck, viral diversity/divergence, immune pressure, and mutations of HLA class I/II restricted epitopes. HCV infection started with transmission bottleneck in all HIV-infected individuals. During the 1.0-2.0 years of infection there was a shift of viral quasispecies in majority of the subjects from one to next visit. However, HCV diversity, divergence, mutations in HLA class I/II restricted and virus neutralizing epitopes were similar in all subjects regardless of CD4 cell count at the time of HCV infection. Our results suggest that HCV transmission and evolution in HIV-infected subjects may not be influenced by host CD4 cell count at the time of infection.
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RIP3 overexpression sensitizes human breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.
Acta Pharmacol. Sin.
PUBLISHED: 01-03-2014
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Receptor-interacting protein 3 (RIP3) is involved in tumor necrosis factor receptor signaling, and results in NF-?B-mediated prosurvival signaling and programmed cell death. The aim of this study was to determine whether overexpression of the RIP3 gene could sensitize human breast cancer cells to parthenolide in vitro.
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Risk of treatment-related deaths with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis of 41 randomized controlled trials.
Onco Targets Ther
PUBLISHED: 01-01-2014
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Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have widely been used in advanced cancer. However, these drugs may also lead to serious adverse events. The present meta-analysis aimed to determine the overall incidence and risk of deaths due to VEGFR-TKIs with more detailed subgroup analysis.
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Familial correlations of onset age of hepatocellular carcinoma: a population-based case-control family study.
PLoS ONE
PUBLISHED: 01-01-2014
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There was lack of evidence for familial aggregation in onset age of hepatocellular carcinoma (HCC) in Chinese population. We conducted a population-based case-control family study to examine familial correlation of age of HCC onset in Taixing, China.
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Effects of domain-specific noise on visual motion processing in schizophrenia.
PLoS ONE
PUBLISHED: 01-01-2014
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Visual perception impairments in schizophrenia stem from abnormal information processing. Information processing requires neural response to a stimulus (signal) against a backdrop of 1) random variation in baseline neural activity (internal noise) and sometimes irrelevant environmental stimulation (external noise). Filtering out noise is a critical aspect of information processing, and needs to be critically examined in schizophrenia.
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The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain.
PLoS ONE
PUBLISHED: 01-01-2014
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The majority of HIV-1 strains enter CD4+ T cells using the CCR5 and/or CXCR4 co-receptor. However, we recently identified a transmitted/founder (T/F) virus (ZP6248) that efficiently used an alternative coreceptor GPR15, rather than commonly used CXCR4 and CCR5, to establish clinical infection. To understand which regions in the env gene were critical for the atypical coreceptor usage, we generated a set of V3 mutants and determined their infectivity in GHOST cells that expressed different coreceptors. When the variable loop 3 (V3) in YU2 was replaced with the ZP6248 V3 (YU2.6248V3), the chimera YU2.6248V3 infected GPR15+ cells but not CCR5+ cells. To determine which amino acids in V3 was responsible for this phenotype change, each of the eight amino acids that differed from the subtype B consensus V3 was substituted with alanine. The G306A and S322A mutations significantly reduced the replication capacity of YU2.6248V3 in GPR15+ cells, while all other alanine substitutions at positions 307, 314, 315, 316, 317 and 318 completely abrogated the infectivity of YU2.6248V3 in GPR15+ cells. The E314A mutation, as the E314G mutation reported before, also rendered the YU2.6248V3 infectious in CCR5+ cells, while none of other alanine mutants could infect CCR5+ cells. These results demonstrated that amino acids in ZP6248 V3 might form a unique conformation that was critical for the interaction with GPR15 while the amino acids at position 314 in the V3 crown of ZP6248 played a key role in interaction with both CCR5 and GPR15. The unique phenotypes of ZP6248 can serve as a model to understand how HIV-1 explores the diverse coreceptor reservoir through novel genetic variants to establish clinical infection.
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Decomposition of organic carbon in fine soil particles is likely more sensitive to warming than in coarse particles: an incubation study with temperate grassland and forest soils in northern China.
PLoS ONE
PUBLISHED: 01-01-2014
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It is widely recognized that global warming promotes soil organic carbon (SOC) decomposition, and soils thus emit more CO2 into the atmosphere because of the warming; however, the response of SOC decomposition to this warming in different soil textures is unclear. This lack of knowledge limits our projection of SOC turnover and CO2 emission from soils after future warming. To investigate the CO2 emission from soils with different textures, we conducted a 107-day incubation experiment. The soils were sampled from temperate forest and grassland in northern China. The incubation was conducted over three short-term cycles of changing temperature from 5°C to 30°C, with an interval of 5°C. Our results indicated that CO2 emissions from sand (>50 µm), silt (2-50 µm), and clay (<2 µm) particles increased exponentially with increasing temperature. The sand fractions emitted more CO2 (CO2-C per unit fraction-C) than the silt and clay fractions in both forest and grassland soils. The temperature sensitivity of the CO2 emission from soil particles, which is expressed as Q10, decreased in the order clay>silt>sand. Our study also found that nitrogen availability in the soil facilitated the temperature dependence of SOC decomposition. A further analysis of the incubation data indicated a power-law decrease of Q10 with increasing temperature. Our results suggested that the decomposition of organic carbon in fine-textured soils that are rich in clay or silt could be more sensitive to warming than those in coarse sandy soils and that SOC might be more vulnerable in boreal and temperate regions than in subtropical and tropical regions under future warming.
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The CUL7/F-box and WD Repeat Domain Containing 8 (CUL7/Fbxw8) Ubiquitin Ligase Promotes Degradation of Hematopoietic Progenitor Kinase 1.
J. Biol. Chem.
PUBLISHED: 12-20-2013
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HPK1, a member of mammalian Ste20-like serine/threonine kinases, is lost in >95% pancreatic cancer through proteasome-mediated degradation. However, the mechanism of HPK1 loss has not been defined. The aims of this study are to identify the ubiquitin ligase and to examine the mechanisms that targets HPK1 degradation. We found that the CUL7/Fbxw8 ubiquitin ligase targeted HPK1 for degradation via the 26S proteasome. The ubiquitination of HPK1 required its kinase activity and autophosphorylation. Wild-type protein phosphatase 4 (PP4), but not the phosphatase-dead PP4 mutant, PP4-RL, inhibits the interaction of Fbxw8 with HPK1 and Fbxw8-mediated ubiquitination of HPK1. In addition, we showed that Thr355 of HPK1 is a key PP4 dephosphorylation site, through which CUL7/Fbxw8 ubiquitin ligase and PP4 regulates HPK1 stability. Knockdown of Fbxw8 restores endogenous HPK1 protein expression and inhibits cell proliferation of pancreatic cancer cells. Our study demonstrated that targeted degradation of HPK1 by the CUL7/Fbxw8 ubiquitin ligase constitutes a negative-feedback loop to restrain the activity of HPK1 and that CUL7/Fbxw8 ubiquitin ligase promotes pancreatic cancer cell proliferation. CUL7/Fbxw8 ubiquitin ligase-mediated HPK1 degradation revealed a direct link and novel role of CUL7/Fbxw8 ubiquitin ligase in the MAPK pathway, which plays a critical role in cell proliferation and differentiation.
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AOPPs Induce MCP-1 Expression by Increasing ROS-Mediated Activation of the NF-?B Pathway in Rat Mesangial Cells: Inhibition by Sesquiterpene Lactones.
Cell. Physiol. Biochem.
PUBLISHED: 11-26-2013
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Background: Monocyte chemoattractant protein-1 (MCP-1) plays an important role in extracellular matrix accumulation through macrophage recruitment and activation in the development and progression of diabetic nephropathy. Therefore, this study examined whether advanced oxidation protein products (AOPPs) are involved in nuclear factor-?B (NF-?B) activation and MCP-1 mRNA and protein expression in mesangial cells (MCs) and evaluated the effects of derivatives of sesquiterpene lactones (SLs) on AOPP-induced renal damage. Methods: MCP-1 mRNA and protein expression in MCs were determined by quantitative real-time PCR and ELISA, respectively. The level of intracellular reactive oxygen species (ROS) was determined by flow cytometry. The protein expression of tubulin, P47, NF-?B p65, phospho-NF-?B p65, I?B, phospho-I?B, IKK? and phospho-IKK? was evaluated by Western blot. Results: AOPPs caused oxidative stress in MCs and activated the NF-?B pathway by inducing I?B? phosphorylation and degradation. Inhibition of ROS by SOD (ROS inhibitor) blocked the AOPP-mediated NF-?B pathway. Moreover, the inhibition of AOPP-induced overproduction of MCP-1 mRNA and protein was associated with inhibition of I?B? degradation by SLs. Conclusion: AOPPs induce MCP-1 expression by activating the ROS/NF-?B pathway and can be inhibited by SLs. These findings may provide a novel approach to treat inflammatory and immune renal diseases, including diabetic nephropathy. © 2014 S. Karger AG, Basel.
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Factors associated with vitamin D deficiency in a Norwegian population: the HUNT Study.
J Epidemiol Community Health
PUBLISHED: 11-06-2013
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Vitamin D deficiency occurs worldwide. Winter season and high Body Mass Index (BMI) are associated with low levels of serum 25-hydroxyvitamin D (25(OH)D). We estimated the prevalence of vitamin D deficiency in a Norwegian adult population and examined factors associated with vitamin D deficiency. A cohort of 25?616 adults (19-55 years) who participated in both the second and third Nord-Trøndelag Health Study (HUNT 2 (1995-1997) and HUNT 3 (2006-2008)) was established in a previous study. A 10% random sample of the cohort population was recruited for serum 25(OH)D measurements (n=2584), which was used for the current cross-sectional study. Vitamin D deficiency was defined as serum 25(OH)D level <50 nmol/L. The overall prevalence of vitamin D deficiency was 40%, but varied by season (winter: 64%; summer: 20%). Winter season (adjusted prevalence ratio (PR): 3.16, 95% CI 2.42 to 4.12) and obesity (BMI ?30.0 kg/m(2)) (PR: 1.74, 95% CI 1.45 to 2.10) were strongly associated with prevalent vitamin D deficiency. Current smoking also demonstrated an increased PR (1.41, 95% CI 1.21 to 1.65). Daily intake of cod liver oil (PR: 0.60, 95% CI 0.41 to 0.77), increased physical activity (PR: 0.80, 95% CI 0.68 to 0.95) and more frequent alcohol consumption (PR: 0.76, 95% CI 0.60 to 0.95) were associated with a reduced PR. The prevalence of vitamin D deficiency was high in Norwegian adults. Winter season, high BMI and current smoking were positively associated, and intake of cod liver oil, increased physical activity and more frequent alcohol consumption were inversely associated with vitamin D deficiency.
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Theoretical study of mononuclear nickel(I), nickel(0), copper(i), and cobalt(I) dioxygen complexes: new insight into differences and similarities in geometry and bonding nature.
Inorg Chem
PUBLISHED: 11-06-2013
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Geometries, bonding nature, and electronic structures of (N^N)Ni(O2) (N^N = ?-diketiminate), its cobalt(I) and copper(I) analogues, and (Ph3P)2Ni(O2) were investigated by density functional theory (DFT) and multistate restricted active space multiconfigurational second-order perturbation (MS-RASPT2) methods. Only (N^N)Ni(O2) takes a C(S) symmetry structure, because of the pseudo-Jahn-Teller effect, while all other complexes take a C(2V) structure. The symmetry lowering in (N^N)Ni(O2) is induced by the presence of the singly occupied ?(d(xy)-?(x)*) orbital. In all of these complexes, significant superoxo (O2-) character is found from the occupation numbers of natural orbitals and the O-O ?* bond order, which is independent of the number of d electrons and the oxidation state of metal center. However, this is not a typical superoxo species, because the spin density is not found on the O2 moiety, even in open-shell complexes, (N^N)Ni(O2) and (N^N)Co(O2). The M-O and O-O distances are considerably different from each other, despite the similar superoxo character. The M-O distance and the interaction energy between the metal and O2 moieties are determined by the d(yz) orbital energy of the metal moiety taking the valence state. The binding energy of the O2 moiety is understood in terms of the d(yz) orbital energy in the valence state and the promotion energy of the metal moiety from the ground state to the valence state. Because of the participations of various charge transfer (CT) interactions between the metal and O2 moieties, neither the d(yz) orbital energy nor the electron population of the O2 moiety are clearly related to the O-O bond length. Here, the ? bond order of the O2 moiety is proposed as a good measure for discussing the O-O bond length. Because the d electron configuration is different among these complexes, the CT interactions are different, leading to the differences in the ? bond order and, hence, the O-O distance among these complexes. The reactivity of dioxygen complex is discussed with the d(yz) orbital energy.
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Identification of Lysine Succinylation Substrates and the Succinylation Regulatory Enzyme CobB in Escherichia coli.
Mol. Cell Proteomics
PUBLISHED: 10-31-2013
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Lysine succinylation is a newly identified protein post-translational modification pathway present in both prokaryotic and eukaryotic cells. However, succinylation substrates and regulatory enzyme(s) remain largely unknown, hindering the biological study of this modification. Here we report the identification of 2,580 bacterial lysine succinylation sites in 670 proteins and 2,803 lysine acetylation (Kac) sites in 782 proteins, representing the first lysine succinylation dataset and the largest Kac dataset in wild-type E. coli. We quantified dynamic changes of the lysine succinylation and Kac substrates in response to high glucose. Our data showed that high-glucose conditions led to more lysine-succinylated proteins and enhanced the abundance of succinyllysine peptides more significantly than Kac peptides, suggesting that glucose has a more profound effect on succinylation than on acetylation. We further identified CobB, a known Sir2-like bacterial lysine deacetylase, as the first prokaryotic desuccinylation enzyme. The identification of bacterial CobB as a bifunctional enzyme with lysine desuccinylation and deacetylation activities suggests that the eukaryotic Kac-regulatory enzymes may have enzymatic activities on various lysine acylations with very different structures. In addition, it is highly likely that lysine succinylation could have unique and more profound regulatory roles in cellular metabolism relative to lysine acetylation under some physiological conditions.
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[Effect of PCI-32765 and Bortezomib on Proliferation and Apoptosis of B-cell Tumor Cell Lines and Its Mechanisms].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-26-2013
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This study was aimed to investigate the effect of Btk inhibitor PCI-32765 and the proteasome inhibitor bortezomib on Raji and Ramos cell proliferation, apoptosis, and its mechanisms. Raji and Ramos cells were treated with PCI-32765 and bortezomib alone and/or their combination. The cell proliferation and apoptosis were detected by CCK-8 and flow cytometry respectively, the expression level of Btk,NF?B, c-IAP1, Bcl-xL and caspase-3 protein were measured by Western blot. The results indicated that: (1) after Raji and Ramos cells were treated with PCI-32765 (0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0 µmol/L) alone and bortezomib (10, 20, 30, 40, 50, 60, 80 nmol/L) alone and their combination for 48 h, the cell proliferation and vitality were inhibited in a dose-dependent manner and both had synergistic effect; (2) Raji and Ramos cells were treated with PCI-32765 (2.0 µmol/L) and bortezomib (20 nmol/L) alone and their combination for 8, 12, 24, 36, 48 and 72 h, the cell proliferation and vitality were inhibited in a time-dependent manner, the two drugs displayed a synergistic effects; (3) the Raji and Ramos cells were treated with PCI-32765 (2.0 µmol/L) and bortezomib (20 nmol/L) alone and their combination for 48 h, all these treatments could induce significant apoptosis of Raji and Ramos cells.In Raji cell experiment, the cell apoptosis rate in the control group, PCI-32765 group, bortezomib group and PCI-32765 and bortezomib combination group were 10.34 ± 0.53%, 24.26 ± 0.91%, 43.66 ± 1.08% and 74.06 ± 0.72% respectively, and the differences was statistically significant among the different groups (P < 0.05). In Ramos cell experiment, the cell apoptosis rate in the control group, PCI-32765 group, bortezomib group and PCI-32765 and bortezomib combination group are 15.16 ± 1.49%, 71.36 ± 0.82%, 75.32 ± 2.36% and 84.30 ± 0.91% respectively, the differences was statistically significant among the different groups (P < 0.05); (4) PCI-32765 and bortezomib could inhibit the expression level of intracellular Btk, NF?B, Bcl-xl and c-IAP1 proteins, but up-regulate the expression level of caspase-3. It is concluded that PCI-32765 and bortezomib can synergistically inhibit the proliferation and induce apoptosis of Raji and Ramos cells, the mechanism may be associated with inhibition of Btk and NF?B activity, down-regulation of anti-apoptotic proteins expression, such as Bcl-xl and c-IAP1, and increase of caspase-3 expression.
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Protection-group-free semisyntheses of parthenolide and its cyclopropyl analogue.
J. Org. Chem.
PUBLISHED: 09-27-2013
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Parthenolide showed extensive bioactivities including selective eradication of AML stem cells. Herein we report protection-free semisyntheses of parthenolide and its cyclopropyl analogue (compound 10) from the abundant natural product costunolide with an overall yield of 55 and 60%, respectively. Compound 10 was more stable than parthenolide, and it maintained comparable activities against AML cell lines and AML stem cells. Therefore, compound 10 might be a superior small molecule than parthenolide as a tool for investigation of cancer stem cell biology.
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A constructed HLA-A2-restricted pMAGE-A1278-286 tetramer detects specific cytotoxic T lymphocytes in tumour tissues in situ.
J. Int. Med. Res.
PUBLISHED: 09-26-2013
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To construct a human leucocyte antigen (HLA)-A2-restricted peptide 278-286 of melanoma-associated antigen family A, 1 (pMAGE-A1278-286) tetramer to analyse the distribution of cytotoxic T lymphocytes (CTLs) in tumour tissue and tumour-adjacent normal tissue.
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Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-?B activation and MCP-1 and TGF-?1 expression in rat mesangial cells.
Molecules
PUBLISHED: 09-12-2013
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Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-?1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-?1 gene expression, western blot to detect the level of I?B? protein and EMSA to measure the activation of nuclear factor kappa B (NF-?B). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-?B, the degradation of I?B?, and the expression of MCP-1, TGF-?1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN.
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SILAC-based quantification of Sirt1-responsive lysine acetylome.
Methods Mol. Biol.
PUBLISHED: 09-10-2013
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Stable Isotope Labeling by Amino acids in Cell culture (SILAC) is one of the in vivo metabolic labeling methods widely used for dynamic analysis of protein modifications. Here, we describe a general approach to applying SILAC, in combination with affinity enrichment of acetyllysine peptides and mass spectrometry, to study the dynamic changes of the Lysine acetylome in response to Sirt1. The method should be applicable to quantify changes to other post translational modifications in diverse cellular systems.
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Gastrin and D1 dopamine receptor interact to induce natriuresis and diuresis.
Hypertension
PUBLISHED: 09-09-2013
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Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl. Gastrin is the major gastrointestinal hormone taken up by renal proximal tubule (RPT) cells. We hypothesized that renal gastrin and dopamine receptors interact to synergistically increase sodium excretion, an impaired interaction of which may be involved in the pathogenesis of hypertension. In Wistar-Kyoto rats, infusion of gastrin induced natriuresis and diuresis, which was abrogated in the presence of a gastrin (cholecystokinin B receptor [CCKBR]; CI-988) or a D1-like receptor antagonist (SCH23390). Similarly, the natriuretic and diuretic effects of fenoldopam, a D1-like receptor agonist, were blocked by SCH23390, as well as by CI-988. However, the natriuretic effects of gastrin and fenoldopam were not observed in spontaneously hypertensive rats. The gastrin/D1-like receptor interaction was also confirmed in RPT cells. In RPT cells from Wistar-Kyoto but not spontaneously hypertensive rats, stimulation of either D1-like receptor or gastrin receptor inhibited Na(+)-K(+)-ATPase activity, an effect that was blocked in the presence of SCH23390 or CI-988. In RPT cells from Wistar-Kyoto and spontaneously hypertensive rats, CCKBR and D1 receptor coimmunoprecipitated, which was increased after stimulation of either D1 receptor or CCKBR in RPT cells from Wistar-Kyoto rats; stimulation of one receptor increased the RPT cell membrane expression of the other receptor, effects that were not observed in spontaneously hypertensive rats. These data suggest that there is a synergism between CCKBR and D1-like receptors to increase sodium excretion. An aberrant interaction between the renal CCK?BR and D1-like receptors (eg, D1 receptor) may play a role in the pathogenesis of hypertension.
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The joint association of anxiety, depression and obesity with incident asthma in adults: the HUNT study.
Int J Epidemiol
PUBLISHED: 09-05-2013
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Anxiety or depression symptoms may increase the risk of developing asthma, and their interaction with obesity is not known. We aimed to assess the association of anxiety or depression symptoms and the joint association of these symptoms and obesity with incident asthma.
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Functional analyses of a flavonol synthase-like gene from Camellia nitidissima reveal its roles in flavonoid metabolism during floral pigmentation.
J. Biosci.
PUBLISHED: 08-14-2013
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The flavonoids metabolic pathway plays central roles in floral coloration, in which anthocyanins and flavonols are derived from common precursors, dihydroflavonols. Flavonol synthase (FLS) catalyses dihydroflavonols into flavonols, which presents a key branch of anthocyanins biosynthesis. The yellow flower of Camellia nitidissima Chi. is a unique feature within the genus Camellia, which makes it a precious resource for breeding yellow camellia varieties. In this work, we characterized the secondary metabolites of pigments during floral development of C. nitidissima and revealed that accumulation of flavonols correlates with floral coloration. We first isolated CnFLS1 and showed that it is a FLS of C. nitidissima by gene family analysis. Second, expression analysis during floral development and different floral organs indicated that the expression level of CnFLS1 was regulated by developmental cues, which was in agreement with the accumulating pattern of flavonols. Furthermore, over-expression of CnFLS1 in Nicotiana tabacum altered floral colour into white or light yellow, and metabolic analysis showed significant increasing of flavonols and reducing of anthocyanins in transgenic plants. Our work suggested CnFLS1 plays critical roles in yellow colour pigmentation and is potentially a key point of genetic engineering toward colour modification in Camellia.
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[Establishment and preliminary application of dengue virus envelope domain III IgG antibody capture enzyme-linked immuno-absorbent assay].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 08-10-2013
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To establish a highly sensitive and specific assay to detect dengue virus (DENV) envelope protein domain III (EDIII) IgG antibody, and to explore its value in the diagnosis and seroepidemiological survey of dengue.
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Rubisco decrease is involved in chloroplast protrusion and Rubisco-containing body formation in soybean (Glycine max.) under salt stress.
Plant Physiol. Biochem.
PUBLISHED: 08-07-2013
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Salt stress often induces declination of net photosynthetic rate (Pn), partially resulted from Rubisco degradation. The chloroplast protrusions (CPs) is one of the pathways of Rubisco exclusion from chloroplasts. To explore the relationship between the Rubisco contents and CPs under salt stress, Pn, maximum photochemical efficiency of PSII (Fv/Fm), carboxylation efficiency (CE) and concentration of Rubisco, number of CPs and Rubisco-containing Body (RCBs) were investigated with two differently salt-responding varieties in this experiment. We observed that 150 mM salt treatment resulted in not only significant decrease in Pn, CE and Rubisco content, but also obvious increase in the number of CPs and RCBs in salt-sensitive variety. Under salt stress formation of CPs resulted in production of much more RCBs, which could immigrate into and combine with vacuole. It may be a kind of important mechanism for rapid degradation of Rubisco under salt stress. Our conclusion provides a new sight for how Rubisco can be fast degraded under salt stress.
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LC-MS/MS quantification of N-acetylneuraminic acid, N-glycolylneuraminic acid and ketodeoxynonulosonic acid levels in the urine and potential relationship with dietary sialic acid intake and disease in 3- to 5-year-old children.
Br. J. Nutr.
PUBLISHED: 08-05-2013
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Red meat and dairy products contain high sialic acid (Sia) levels, but the metabolic fate and health impact in children remain unknown. The aims of the present study were to quantify the levels of urinary Sia N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc) and ketodeoxynonulosonic acid (KDN) and to determine their relationship with dietary Sia intake. Spot urine samples were collected from 386 healthy children aged 3 (n 108), 4 (n 144) and 5 (n 134) years at 06.30-07.00, 11.30-12.00 and 16.30-17.00 hours. Food intake levels were recorded on the day of urine sample collection. Sia levels were quantified using LC-MS/MS with [13C3]Sia as an internal standard. We found that (1) total urinary Sia levels in healthy pre-school children ranged from 40 to 79 mmol Sia/mol creatinine; (2) urinary Sia levels were independent of age and consisted of conjugated Neu5Ac (approximately 70·8 %), free Neu5Ac (approximately 21·3 %), conjugated KDN (approximately 4·2 %) and free KDN (approximately 3·7 %); Neu5Gc was detected in the urine of only one 4-year-old girl; (3) total urinary Sia levels were highest in the morning and declined over time in 4- and 5-year-old children (P< 0·05), but not in 3-year-old children; (4) Sia intake levels at breakfast and lunch were approximately 2·5 and 0·16 mg Sia/kg body weight; and (5) there was no significant correlation between dietary Sia intake levels and urinary Sia levels. Urinary Sia levels varied with age and time of day, but did not correlate with Sia intake in 3- to 5-year-old children. The difference in urinary Sia levels in children of different age groups suggests that the metabolism and utilisation rates of dietary Sia are age dependent.
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Hypertension, fluid overload and micro inflammation are associated with left ventricular hypertrophy in maintenance hemodialysis patients.
Ren Fail
PUBLISHED: 08-01-2013
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This cross-sectional study aims to identify the potential risk factors of left ventricular hypertrophy (LVH) in hemodialysis (HD) patients. Echocardiography, anthropometric measurements and biochemical analyses were performed for 112 HD patients. In univariate analysis, body mass index, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, glycated albumin, high sensitivity C-reactive protein (hs-CRP), cardiac troponin T (cTnT), amino-terminal pro-B-natriuretic peptide (NT-proBNP) and carotid artery intima-media thickness were positively correlated with left ventricular mass index (LVMI); pre-albumin, serum creatinine, left ventricular ejection fraction (LVEF) and fractional shortening were negatively correlated with LVMI. Linear regression analysis showed systolic blood pressure, NT-proBNP and LVEF were independently associated with LVMI. According to a binary logistic regression model, higher systolic blood pressure, NT-proBNP and hs-CRP levels showed independent correlation with LVH. Receiver operator characteristic curves analysis showed the associations between NT-proBNP and LVH more closely than hs-CRP and cTnT. The area under the curve for NT-proBNP, hs-CRP and cTnT was 0.762 (95% CI: 0.660-0.864, p?
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Whartons jelly-derived mesenchymal stem cells promote myocardial regeneration and cardiac repair after miniswine acute myocardial infarction.
Coron. Artery Dis.
PUBLISHED: 07-30-2013
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To investigate the therapeutic effects of Whartons jelly-derived mesenchymal stem cells (WJ-MSCs) on myocardial regeneration and cardiac repair after acute myocardial infarction (AMI).
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Identification of inhibitors of the antibiotic-resistance target New Delhi metallo-?-lactamase 1 by both nanoelectrospray ionization mass spectrometry and ultrafiltration liquid chromatography/mass spectrometry approaches.
Anal. Chem.
PUBLISHED: 07-30-2013
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Mass spectrometry-based platforms have gained increasing success in discovery of ligands bound to therapeutic targets as drug candidates. We established both a nanoelectrospray ionization mass spectrometry (nanoESI-MS) assay and an ultrafiltration liquid chromatography/mass spectrometry (LC/MS) assay to identify new ligands for New Delhi metallo-?-lactamase 1 (NDM-1), responsible for worldwide antibiotic resistance. To alleviate nonspecific binding of hydrophobic compounds and eliminate false positives typically encountered in the indirect LC/MS-based assay, we introduced a blocking protein in the control, which remarkably enhances the selectivity and accuracy of the indirect approach. Side-by-side comparison of the two MS-based approaches for the first time further reveals unique advantages of the indirect approach, including better reproducibility and tolerance of interference. Moreover, the success of fishing out a potent ligand from a mixture of small-molecule fragments demonstrates great potential of the indirect LC/MS-based approach for constructing a robust screening platform against combinatorial libraries or natural product extracts. More importantly, by combining the results of MS-based analyses, enzymatic activity assay, competition experiments, and structural simulation, we discovered a new compound as a promising drug candidate targeting NDM-1.
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