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Find video protocols related to scientific articles indexed in Pubmed.
Allopurinol treatment improves renal function in patients with type 2 diabetes and asymptomatic hyperuricemia: a three years of randomized parallel-controlled study.
Clin. Endocrinol. (Oxf)
PUBLISHED: 11-18-2014
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To investigate the effects of long-term effective control of serum uric acid on renal function in patients with type 2 diabetes and asymptomatic hyperuricemia.
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Prevalence and Risk Factors for Farmer's Lung in Greenhouse Farmers: An Epidemiological Study of 5,880 Farmers from Northeast China.
Cell Biochem. Biophys.
PUBLISHED: 10-27-2014
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The objectives of this epidemiological study were to evaluate the prevalence of farmer's lung disease (FLD) and to explore the potential risk factors for FLD among Chinese greenhouse farmers. A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of Northeastern China. These farmers participated in the study by answering a medical questionnaire. 5,420 greenhouse farmers accepted and answered questionnaires in full (response rate, 92.18 %). Prevalence of FLD among these farmers was 5.7 % (308/5,420). Besides, a number of classic risk factors for FLD were identified, such as years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m(2) but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, and et al. FLD is and will continue to be a real health problem for Chinese farmers. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers might be greatly reduced.
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Hispidulin Enhances the Anti-Tumor Effects of Temozolomide in Glioblastoma by Activating AMPK.
Cell Biochem. Biophys.
PUBLISHED: 10-16-2014
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Glioblastoma is an aggressive malignancy, which is notorious for its poor prognosis. Although Temozolomide (TMZ) has been showed to be an effective chemotherapeutic agent for glioblastoma treatment, the response rate is far from satisfactory. As a natural compound with anti-cancer activity against a variety of cancers, Hispidulin is a good candidate drug for combination therapy. This study is designed to determine whether Hispidulin could potentiate the anti-tumor activity of TMZ in glioblastoma. Cell proliferation and apoptosis were determined by MTT assay and Hoechst staining, respectively. Expression of proteins relevant to apoptosis and proliferation was detected by Western blotting. Our in vitro assays showed that Hispidulin enhanced the anti-tumor activity of TMZ in glioblastoma by both inhibiting cell proliferation and inducing cell apoptosis. The anti-tumor activity of Hispidulin and the enhanced TMZ anti-tumor activity by Hispidulin induced the activation of AMPK signaling pathway. Our results showed that Hispidulin, by activating AMPK, exhibited anti-tumor activity and potentiated the anti-tumor activity of TMZ in glioblastoma. Although further preclinical and clinical studies are needed, this study provides insight for using Hispidulin as a chemosensitizing agent in clinic settings.
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MECHANISMS IN ENDOCRINOLOGY: Main air pollutants and diabetes-associated mortality: a systematic review and meta-analysis.
Eur. J. Endocrinol.
PUBLISHED: 10-10-2014
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Exposure to high levels of air pollutants may be linked to diabetes-associated mortality, but the associations remain unclear. To assess the associations between main air pollutants and diabetes-associated mortality, a systematic review and meta-analysis was performed.
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MECHANISMS IN ENDOCRINOLOGY: Effect of long-term exposure to air pollution on type 2 diabetes mellitus risk: a systemic review and meta-analysis of cohort studies.
Eur. J. Endocrinol.
PUBLISHED: 10-10-2014
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To assess the effect of long-term exposure to air pollution on type 2 diabetes risk, a meta-analysis of prospective cohort studies was performed.
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Asymmetric domino reaction of cyclic N-sulfonylimines and simple aldehydes with trans-perhydroindolic acid as an organocatalyst.
Org. Lett.
PUBLISHED: 08-20-2014
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An asymmetric domino reaction was developed utilizing readily available cyclic N-sulfonylimines and simple aldehydes to construct biologically important and synthetically challenging piperidine derivatives consisting of three contiguous stereocenters. trans-Perhydroindolic acid proved to be an efficient organocatalyst in this reaction (up to 89% yield, 80:20 dr, and 99% ee). The absolute configuration of the catalytic product was determined by X-ray crystallography studies. The product could be conveniently converted to synthetically useful intermediates, such as (3R,4S)-4-ethyl-3-methyl-6-phenylpiperidinyridin-2-one (8), via a simple transformation.
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Strong association of high urinary iodine with thyroid nodule and papillary thyroid cancer.
Tumour Biol.
PUBLISHED: 08-15-2014
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This study demonstrates a strong association of high urinary iodine with thyroid nodules and papillary thyroid cancer as well as aggressive cancer features, suggesting that high urinary iodine is a risk factor for thyroid cancer. The risk of high iodine intake for thyroid cancer has been suggested but not established. The objective of the study was to evaluate the relationship between urine iodine levels and thyroid nodule and thyroid cancer. We preoperatively tested fasting urine iodine in 154 thyroid nodule patients and correlated the results with pathological diagnoses and compared with 306 subjects as normal control. The median urine iodine (MUI) was 331.33 ?g/L in patients with benign thyroid nodules versus 466.23 ?g/L in patients with papillary thyroid cancer (PTC) (P?=?0.003), both of which were in the excessive iodine state and higher than the MUI of 174.30 ?g/L in the control group (P??300 ?g/L) was seen in 62.75 % of patients with benign thyroid nodules and 66.99 % of patients with PTC, both of which were significantly higher than the iodine excessive rate of 19.93 % in the control group (P?
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Studying the mechanism of CD47-SIRP? interactions on red blood cells by single molecule force spectroscopy.
Nanoscale
PUBLISHED: 07-24-2014
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The interaction forces and binding kinetics between SIRP? and CD47 were investigated by single-molecule force spectroscopy (SMFS) on both fresh and experimentally aged human red blood cells (hRBCs). We found that CD47 experienced a conformation change after oxidation, which influenced the interaction force and the position of the energy barrier between SIRP? and CD47. Our results are significant for understanding the mechanism of phagocytosis of red blood cells at the single molecule level.
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miRNA-130b is required for the ERK/FOXM1 pathway activation-mediated protective effects of isosorbide dinitrate against mesenchymal stem cell senescence induced by high glucose.
Int. J. Mol. Med.
PUBLISHED: 07-15-2014
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The present study was carried out to investigate the hypothesis that organic nitrates can attenuate the senescence of mesenchymal stem cells (MSCs), a superior cell source involved in the regeneration and repair of damaged tissue. MSCs were treated with high glucose (HG) in order to induce senescence, which was markedly attenuated by pre-treatment with isosorbide dinitrate (ISDN), a commonly used nitrate, as indicated by senescence-associated galactosidase (SA-?-gal) activity, p21 expression, as well as by the mRNA levels of DNA methyltransferase 1 (DNMT1) and differentiated embryo chondrocyte expressed gene 1 (DEC1), which are senescence-related biomarkers. It was also found that the senescent MSCs (induced by HG glucose) exhibited a marked downregulation in ERK activity and forkhead box M1 (FOXM1) expression, which was reversed by ISDN preconditioning. Of note, the inhibition of ERK phosphorylation or the downregulation of FOXM1 statistically abolished the favourable effects of ISDN. In addition, the investigation of the senescence-associated miR-130 family suggested that miR-130b mediates the beneficial effects of ISDN; it was found that the protective effects of ISDN against the senescence of MSCs were prominently reversed by the knockdown of miR-130b. Furthermore, the downregulation of ERK phosphorylation or FOXM1 expression decreased the miR-130b expression level; however, the suppression of miR-130b demonstrated no significant impact on ERK phosphorylation or FOXM1 expression. Taken together, to the best of our knowledge, the present study is the first to demonstrate the favourable effects of ISDN against HG-induced MSC senescence, which are mediated through the activation of the ERK/FOXM1 pathway and the upregulation of miR-130b.
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MicroRNAs as Potential Biomarkers for Diagnosing Cancers of Central Nervous System: a Meta-analysis.
Mol. Neurobiol.
PUBLISHED: 06-10-2014
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Recent studies have shown abnormal microRNA (miRNA) expression levels in the central nervous system (CNS) of cancer patients, suggesting that miRNAs may serve as promising biomarkers for cancers of CNS. However, other studies have arrived at conflicting results. Therefore, this meta-analysis aims to systematically measure the potential diagnostic value of miRNAs for CNS cancers. Electronic databases as well as other sources were searched until to April 12, 2014 for relevant articles. Data from different studies were pooled using the random-effects model. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), together with the summary receiver operator characteristic (SROC) curve, and area under the SROC curve (AUC) value were used to estimate overall diagnostic performance. Twenty-three studies from 6 articles were included in the current meta-analysis with a total of 299 CNS cancer patients and 418 controls. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.85 (95 % CI, 0.80-0.89), 0.83 (95 % CI, 0.76-0.88), 5.1 (95 % CI, 3.4-7.5), 0.18 (95 % CI, 0.12-0.26), 28 (95 % CI, 14-58), and 0.91 (95 % CI, 0.88-0.93), respectively. Subgroup analyses showed that cerebrospinal fluid (CSF)-based miRNAs assays yielded more accurate results and seemed to be more sensitive in diagnosing of primary central nervous system lymphoma (PCNSL). In conclusion, miRNAs may be suitable for serving as noninvasive biomarkers for CNS cancers detection. However, further validation based on a larger sample of patients and controls is still required.
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Combined MEK and JAK inhibition abrogates murine myeloproliferative neoplasm.
J. Clin. Invest.
PUBLISHED: 05-08-2014
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Overactive RAS signaling is prevalent in juvenile myelomonocytic leukemia (JMML) and the myeloproliferative variant of chronic myelomonocytic leukemia (MP-CMML) in humans, and both are refractory to conventional chemotherapy. Conditional activation of a constitutively active oncogenic Nras (NrasG12D/G12D) in murine hematopoietic cells promotes an acute myeloproliferative neoplasm (MPN) that recapitulates many features of JMML and MP-CMML. We found that NrasG12D/G12D-expressing HSCs, which serve as JMML/MP-CMML-initiating cells, show strong hyperactivation of ERK1/2, promoting hyperproliferation and depletion of HSCs and expansion of downstream progenitors. Inhibition of the MEK pathway alone prolonged the presence of NrasG12D/G12D-expressing HSCs but failed to restore their proper function. Consequently, approximately 60% of NrasG12D/G12D mice treated with MEK inhibitor alone died within 20 weeks, and the remaining animals continued to display JMML/MP-CMML-like phenotypes. In contrast, combined inhibition of MEK and JAK/STAT signaling, which is commonly hyperactivated in human and mouse CMML, potently inhibited human and mouse CMML cell growth in vitro, rescued mutant NrasG12D/G12D-expressing HSC function in vivo, and promoted long-term survival without evident disease manifestation in NrasG12D/G12D animals. These results provide a strong rationale for further exploration of combined targeting of MEK/ERK and JAK/STAT in treating patients with JMML and MP-CMML.
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A polymeric liquid membrane electrode responsive to 3,3',5,5'-tetramethylbenzidine oxidation for sensitive peroxidase/peroxidase mimetic-based potentiometric biosensing.
Anal. Chem.
PUBLISHED: 04-18-2014
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The oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) has great utility in bioanalysis such as peroxidase/peroxidase mimetic-based biosensing. In this paper, the behaviors of TMB oxidation intermediates/products in liquid/liquid biphasic systems have been investigated for the first time. The free radical, charge transfer complex, and diimine species generated by TMB oxidation are all positively charged under acidic and near-neutral conditions. Electron paramagnetic resonance and visible absorbance spectroscopy data demonstrate that these cationic species can be effectively transferred from an aqueous phase into a water-immiscible liquid phase functionalized by an appropriate cation exchanger. Accordingly, sensitive potential responses of TMB oxidation have been obtained on a cation exchanger-doped polymeric liquid membrane electrode under mildly acidic and near-neutral conditions. By using the membrane electrode responsive to TMB oxidations, two sensitive potentiometric biosensing schemes including the peroxidase-labeled sandwich immunoassay and G-quadruplex DNAzyme-based DNA hybridization assay have been developed. The obtained detection limits for the target antigen and DNA are 0.02 ng/mL and 0.1 nM, respectively. Coupled with other advantages such as low cost, high reliability, and ease of miniaturization and integration, the proposed polymeric liquid membrane electrode holds great promise as a facile and efficient transducer for TMB oxidation and related biosensing applications.
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Cryptotanshinone reverses ovarian insulin resistance in mice through activation of insulin signaling and the regulation of glucose transporters and hormone synthesizing enzymes.
Fertil. Steril.
PUBLISHED: 03-25-2014
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To investigate the effects of cryptotanshinone (CRY), an active component of Chinese medicine, on ovarian androgen production, insulin resistance (IR), and glucose metabolism in mice.
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Palladium-catalyzed allylic alkylation of simple ketones with allylic alcohols and its mechanistic study.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-17-2014
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Allylic alcohols were directly used in Pd-catalyzed allylic alkylations of simple ketones under mild reaction conditions. The reaction proceeded smoothly at 20?°C by the concerted action of a Pd catalyst, a pyrrolidine co-catalyst, and a hydrogen-bonding solvent, and does not require any additional reagents. A computational study suggested that methanol plays a crucial role in the formation of the ?-allylpalladium complex by lowering the activation barrier.
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Hydrogen-bond-activated palladium-catalyzed allylic alkylation via allylic alkyl ethers: challenging leaving groups.
Org. Lett.
PUBLISHED: 03-12-2014
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C-O bond cleavage of allylic alkyl ether was realized in a Pd-catalyzed hydrogen-bond-activated allylic alkylation using only alcohol solvents. This procedure does not require any additives and proceeds with high regioselectivity. The applicability of this transformation to a variety of functionalized allylic ether substrates was also investigated. Furthermore, this methodology can be easily extended to the asymmetric synthesis of enantiopure products (99% ee).
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TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer.
J. Clin. Endocrinol. Metab.
PUBLISHED: 03-11-2014
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Promoter mutations chr5:1,295,228C>T and chr5:1,295,250C>T (termed C228T and C250T, respectively) in the gene for telomerase reverse transcriptase (TERT) have been reported in various cancers and need to be further investigated in thyroid cancer.
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Regional specific regulation of steroid receptor coactivator-1 immunoreactivity by orchidectomy in the brain of adult male mice.
Steroids
PUBLISHED: 02-26-2014
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Androgens including testosterone and dihydrotestosterone play important roles on brain structure and function, either directly through androgen receptor or indirectly through estrogen receptors, which need coactivators for their transcription activation. Steroid receptor coactivator-1 (SRC-1) has been shown to be multifunctional potentials in the brain, but how it is regulated by androgens in the brain remains unclear. In this study, we explored the effect of orchidectomy (ORX) on the expression of SRC-1 in the adult male mice using nickel-intensified immunohistochemistry. The results showed that ORX induced dramatic decrease of SRC-1 immunoreactivity in the olfactory tubercle, piriform cortex, ventral pallidum, most parts of the septal area, hippocampus, substantia nigra (compact part), pontine nuclei and nucleus of the trapezoid body (p<0.01). Significant decrease of SRC-1 was noticed in the dorsal and lateral septal nucleus, medial preoptical area, dorsomedial and ventromedial hypothalamic nucleus and superior paraolivary nucleus (p<0.05). Whereas in other regions examined, levels of SRC-1 immunoreactivity were not obviously changed by ORX (p>0.05). The above results demonstrated ORX downregulation of SRC-1 in specific regions that have been involved in sense of smell, learning and memory, cognition, neuroendocrine, reproduction and motor control, indicating that SRC-1 play pivotal role in the mediating circulating androgenic regulation on these important brain functions. It also indicates that SRC-1 may serve as a novel target for the central disorders caused by the age-related decrease of circulating androgens.
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The problem of unreasonably high pharmaceutical fees for patients in Chinese hospitals: a system dynamics simulation model.
Comput. Biol. Med.
PUBLISHED: 02-22-2014
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The social problem of unreasonably high pharmaceutical costs for patients in Chinese hospitals damages the interests of patients and it has a highly negative impact on the long-term development of the Chinese health service. We constructed a system dynamics model to address two problems, i.e., the unreasonably high prices of drugs and the high level of pharmaceutical fees relative to the medical costs of patients, and we suggest countermeasures and possible solutions. The program Vensim DSS was used to construct a system dynamics model to represent the problem of high pharmaceutical fees for patients in Chinese hospitals. If hospital and medical staff receive a higher kickback rate, they are more likely to prescribe unnecessary expensive drugs to make greater profits, which results in unnecessary drug consumption and irrational drug use, eventually leading to unreasonably high pharmaceutical fees. The benefit chain of the main drug suppliers should be cut off. It is necessary to break the link between the profits from pharmaceutical sales and the prescribing behavior of physicians, and hospital incomes, to avoid any conflicts of interest over how medicines are prescribed. Thus, cost-containment measures and a reformed pharmaceutical distribution system are needed to regulate physicians and hospital interaction.
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Elevated pulmonary artery pressure predicts poor outcome after cardiac resynchronization therapy.
J Interv Card Electrophysiol
PUBLISHED: 02-18-2014
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Pulmonary artery hypertension is correlated with poor clinical prognosis in patients with chronic heart failure. However, there is a paucity of data concerning the impact of baseline pulmonary artery systolic pressure (PASP) on clinical outcome after cardiac resynchronization therapy (CRT). The aim of the study is to evaluate the association of baseline PASP with CRT response.
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Effect and mechanisms of human Wharton's jelly-derived mesenchymal stem cells on type 1 diabetes in NOD model.
Endocrine
PUBLISHED: 02-14-2014
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Type 1 diabetes is an autoimmune disease that results from an inflammatory destruction of ?-cells in islets. Mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) own a peculiar immunomodulatory feature and might reverse the inflammatory destruction and repair the function of ?-cells. Sixty NOD mice were divided into four groups, including normal control group, WJ-MSCs prevention group (before onset), WJ-MSCs treatment group (after onset), and diabetic control group. After homologous therapy, onset time of diabetes, levels of fasting plasma glucose (FPG), fed blood glucose and C-peptide, regulation of cytokines, and islet cells were examined and evaluated. After WJ-MSCs infusion, FPG and fed blood glucose in WJ-MSCs treatment group decreased to normal level in 6-8 days and maintained for 6 weeks. Level of fasting C-peptide of these mice was higher compared to diabetic control mice (P = 0.027). In WJ-MSCs prevention group, WJ-MSCs played a protective role for 8-week delayed onset of diabetes, and fasting C-peptide in this group was higher compared to the other two diabetic groups (P = 0.013, 0.035). Compared with diabetic control group, frequencies of CD4(+)CD25(+)Foxp3(+) Tregs in WJ-MSCs prevention group and treatment group were higher, while levels of IL-2, IFN-?, and TNF-? were lower (P < 0.001); the degree of insulitis was also depressed, especially for WJ-MSCs prevention group(P < 0.05). Infusion of WJ-MSCs could aid in T1DM through regulation of the autoimmunity and recovery of islet ?-cells no matter before or after onset of T1DM. WJ-MSCs might be an effective method for T1DM.
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Exploring cross-talk between oxidative damage and excitotoxicity and the effects of riluzole in the rat cortex after exposure to methylmercury.
Neurotox Res
PUBLISHED: 02-12-2014
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Methylmercury (MeHg) is a ubiquitous environmental toxin that causes neurologic and developmental diseases. Oxidative damage and excitotoxicity are putative mechanisms, which underlie MeHg-induced neurotoxicity. In this study, the cross-talk between the oxidative damage and excitotoxicity pathways and the protective effects of riluzole in the rat cortex were explored. Rats were injected with MeHg and/or riluzole, and cold vapor atomic fluorescence spectrometry, hematoxylin and eosin staining, flow cytometry, fluorescence assays, spectrophotometry, real-time PCR, and Western blotting were used to evaluate neurotoxicity. The present study showed that (1) MeHg accumulated in the cerebral cortex and caused pathology. (2) MeHg caused oxidative damage by inducing glutathione (GSH) depletion, reactive oxygen species (ROS) production, inhibition of antioxidant enzyme activity, and alteration of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. (3) MeHg disrupted the glutamate transporters (GluTs), glutamate-glutamine cycle, and N-methyl-D-aspartate receptor expression and induced excitotoxicity. (4) Excitotoxicity resulted in disruption of GSH synthesis, calcium overloading, oxidative damage, and excessive ROS production. (5) Pretreatment with riluzole antagonized MeHg neurotoxicity by down regulating cross-talk between the oxidative damage and excitotoxicity pathways. In conclusion, the cross-talk between the oxidative damage and excitotoxicity pathways caused by MeHg exposure was linked by GluTs and calcium and inhibited by riluzole treatment.
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Expression of estrogen receptors, androgen receptor and steroid receptor coactivator-3 is negatively correlated to the differentiation of astrocytic tumors.
Cancer Epidemiol
PUBLISHED: 01-25-2014
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Astrocytic tumors are the most common primary brain tumors. It has been reported that androgen receptor (AR), estrogen receptors alpha (ER?) and beta (ER?) and their coactivator SRC-1 and SRC-3 are involved in the regulation of the growth and development of many tumors, but their expression profiles and significances in the astrocytic tumors remain largely unknown. In this study, the expression of AR, ERs, and SRCs, and the possible roles of them in astrocytic neoplasm were evaluated and compared to normal brain tissues by nickel-intensified immunohistochemistry with tissue microarrays. The results showed that there were no age- or gender-differences regarding to the levels of these receptors or coactivators in astrocytic or normal brain tissues. In the high-grade astrocytic tissue, the levels of AR, ERs and SRC-3 were significantly decreased when compared to the low-grade astrocytic tissues, but the levels of SRC-1 remain unchanged. Correlation analysis revealed that the levels of AR, ERs and SRC-3 were negatively correlated to tumor differentiation, and the levels of SRC-3 were positively correlated to that of ER?. Furthermore, the decreased levels of SRC-3 were associated with an increase of ER? in astrocytic tumors when compared to that of normal brain tissues. These above results indicate a combination of decreased expression of ERs, AR and SRC-3 but not SRC-1 may be involved in the tumorigenesis of gliomas, ER?/SRC-3 axis may play central role in the regulation these tumors.
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Emergence of canine distemper virus strains with two amino acid substitutions in the haemagglutinin protein, detected from vaccinated carnivores in North-Eastern China in 2012-2013.
Vet. J.
PUBLISHED: 01-15-2014
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A total of 16 strains of canine distemper virus (CDV) were detected from vaccinated minks, foxes, and raccoon dogs in four provinces in North-Eastern China between the end of 2011 and 2013. Upon sequence analysis of the haemagglutinin gene and comparison with wild-type CDV from different species in the same geographical areas, two non-synonymous single nucleotide polymorphisms were identified in 10 CDV strains, which led to amino acid changes at positions 542 (isoleucine to asparagine) and 549 (tyrosine to histidine) of the haemagglutinin protein coding sequence. The change at residue 542 generated a potentially novel N-glycosylation site. Masking of antigenic epitopes by sugar moieties might represent a mechanism for evasion of virus neutralising antibodies and reduced protection by vaccination.
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Intriguing roles of hippocampus-synthesized 17?-estradiol in the modulation of hippocampal synaptic plasticity.
J. Mol. Neurosci.
PUBLISHED: 01-14-2014
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Accumulated studies have shown that 17?-estradiol (E2) can be de novo synthesized in the hippocampus, and its role in the regulation of hippocampal synaptic plasticity, which is the basis of learning and memory, has long been exploring. Steroidogenic enzymes (e.g., aromatase) that are essential to the hippocampus-synthesized synthesis of E2 have been detected in the hippocampus. Inhibition of E2 synthesis by aromatase inhibitors significantly reduces the density of hippocampal spine synapses, levels of some synaptic proteins such as spinopholin and synaptophysin. Moreover, the electrophysiological properties of hippocampal neurons are also changed in response to this inhibition. The influences of gonadal and hippocampal E2 on synaptic plasticity may exist some differences, since some reports showed that gonadal (or circulating) estrogens have no obvious effects in the modulation of hippocampal synaptic proteins as evidenced in some ovariectomized animals and postmenopausal women who suffered from Alzheimer's disease (AD). These evidences leads to a hypothesis that hippocampal E2 may play a more important role in modulation of synaptic plasticity than gonadal E2. The signaling pathways, whereby hippocampal E2 modulates synaptic plasticity, insist of classical chronic genomic pathway and rapid nongenomic pathway, which mediated by nonnuclear estrogen receptor (GPER) and/or nuclear or nonnuclear estrogen receptors, which require coactivators for their transcription activity. Among which steroid receptor coactivator-1 (SRC-1) is the predominant coactivator p160 family members in the brain. Several clues have shown that SRC-1 is expressed in hippocampus and is highly correlated with some key synaptic proteins developmentally or after orchidectomy but not ovariectomy, indicating SRC-1 may be regulated by hippocampus-synthesized E2 and profoundly involved in the mediation of hippocampal E2 regulation of hippocampal synaptic plasticity. Further studies about the exact roles of hippocampus-synthesized E2 and therefore SRC-1 are urgently needed in order to facilitate our understanding of hippocampal E2, which will be very important to the development of novel strategies of estrogen replacement therapy against neurodegenerative deficits such as Alzheimer's disease (AD).
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Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocrine and integration.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 01-13-2014
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As one of the third generation of aromatase inhibitors, letrozole is a favored drug for the treatment of hormone receptor-positive breast cancer with some adverse effects on the nervous system, but the knowledge is limited and the results are controversial, the mechanism underlying its central action is also unclear. Accumulated evidences have demonstrated that estrogens derived from androgens by aromatase play profound roles in the brain through their receptors, which needs coactivator for the transcription regulation, among which steroid receptor coactivator-1 (SRC-1) has been shown to be multifunctional potentials in the brain, but whether it is regulated by letrozole is currently unknown. In this study, we examined letrozole regulation on SRC-1 expression in adult mice brain using immunohistochemistry. The results showed that letrozole induced dramatic decrease of SRC-1 in the medial septal, hippocampus, medial habenular nucleus, arcuate hypothalamic nucleus and superior colliculus (p<0.01). Significant decrease was detected in the dorsal lateral septal nucleus, bed nucleus of stria terminalis, ventral taenia tecta, dorsomedial and ventromedial hypothalamic nuclei, dorsomedial periaqueductal gray, superior paraolivary nucleus and pontine nucleus (p<0.05). In the hippocampus, levels of estradiol content, androgen receptor, estrogen receptor ? and ? also decreased significantly after letrozole injection. The above results demonstrated letrozole downregulation of SRC-1 in specific regions that are primarily related to learning and memory, cognition and mood, neuroendocrine as well as information integration, indicating that SRC-1 may be one important downstream central target of letrozole. Furthermore, these potential central adverse effects of letrozole should be taken into serious considerations.
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Chuanhu anti-gout mixture versus colchicine for acute gouty arthritis: a randomized, double-blind, double-dummy, non-inferiority trial.
Int J Med Sci
PUBLISHED: 01-01-2014
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The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects.
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Strain effect on the adsorption, diffusion, and molecular dissociation of hydrogen on Mg (0001) surface.
J Chem Phys
PUBLISHED: 12-17-2013
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The adsorption, diffusion, and molecular dissociation of hydrogen on the biaxially strained Mg (0001) surface have been systematically investigated by the first principle calculations based on density functional theory. When the strain changes from the compressive to tensile state, the adsorption energy of H atom linearly increases while its diffusion barrier linearly decreases oppositely. The dissociation barrier of H2 molecule linearly reduces in the tensile strain region. Through the chemical bonding analysis including the charge density difference, the projected density of states and the Mulliken population, the mechanism of the strain effect on the adsorption of H atom and the dissociation of H2 molecule has been elucidated by an s-p charge transfer model. With the reduction of the orbital overlap between the surface Mg atoms upon the lattice expansion, the charge transfers from p to s states of Mg atoms, which enhances the hybridization of H s and Mg s orbitals. Therefore, the bonding interaction of H with Mg surface is strengthened and then the atomic diffusion and molecular dissociation barriers of hydrogen decrease accordingly. Our works will be helpful to understand and to estimate the influence of the lattice deformation on the performance of Mg-containing hydrogen storage materials.
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Experiment research on inhibition of glioma with sTRAIL in vitro.
Artif Cells Nanomed Biotechnol
PUBLISHED: 10-25-2013
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We report that adenovirus mediated TNF-related apoptosis-inducing ligand (TRAIL) influenced the cell growth and cell cycle in the glioma cells in vitro. After being infected with the Ad-sTRAIL, U251 cell growth was inhibited. The expression of sTRAIL was detected using immunofluorescence. The higher rate of apoptosis was demonstrated using short-term microculture tetrazoliun (MTT) assay and flow cytometry. The rate of Ad-sTRAIL-inducing U251 cell apoptosis was increased depending on the dosage and the time. The apoptosis of G0/G1 and S phase cells was more significant than that of the control groups. The growth and proliferation of U251 cell line was inhibited after the infection of Ad-sTRAIL. It is dose- and time dependent.
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P-Stereogenic PCP pincer-Pd complexes: synthesis and application in asymmetric addition of diarylphosphines to nitroalkenes.
Org. Lett.
PUBLISHED: 10-21-2013
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Novel P-stereogenic PCP pincer-Pd complexes were designed and prepared in short steps from optically pure tert-butylmethylphosphine-borane. These optically active Pd-complexes were successfully applied in asymmetric addition of diarylphosphines to nitroalkenes with high yields and good enantioselectivity.
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Impact of interlead distance on immediate and mid-term response to cardiac resynchronization therapy.
Scand. Cardiovasc. J.
PUBLISHED: 08-14-2013
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It is currently recommended that the left ventricular (LV) lead be placed at the posterolateral or lateral wall of heart during cardiac resynchronization therapy (CRT). The aim of our study is to evaluate the influence of interlead distance on immediate and mid-term response to CRT with altered right ventricular (RV) pacing site.
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The force of transporting a single amino acid into the living cell measured using atomic force microscopy.
Chem. Commun. (Camb.)
PUBLISHED: 08-09-2013
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We used single molecule force spectroscopy (SMFS) to investigate the interacting force between single cysteine and amino acid transporters in eukaryotic cell membranes. We measured the transporting force of cysteine and found that its conformation on the AFM tip is important for discriminating the substrate in the transporting pathway.
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Therapeutic role of EF24 targeting glucose transporter 1-mediated metabolism and metastasis in ovarian cancer cells.
Cancer Sci.
PUBLISHED: 08-02-2013
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Cancer cells require glucose to support their rapid growth through a process known as aerobic glycolysis, or the Warburg effect. As in ovarian cancer cells, increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer. However, it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis. In the present research, we found that EF24, a HIF-1? inhibitor, could significantly block glucose uptake, the rate of glycolysis, and lactate production compared with vehicle treatment in SKOV-3, A2780 and OVCAR-3 cells. These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays. Furthermore, as an important mediator of glucose metabolism, glucose transporter 1 (Glut1) was found to contribute to the function of EF24 in both energy metabolism and metastasis. To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model, intraperitoneal metastasis and lung metastasis model were introduced. Our results indicated that EF24 treatment could inhibit tumor growth, intraperitoneal metastasis and lung metastasis of SKOV-3 cells, and Glut1 is a possible mediator for the role of EF24. In conclusion, our results highlight that an anti-cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis, and EF24 is a possible candidate for anti-metastasis therapeutic applications for ovarian cancer.
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Palladium-catalyzed asymmetric hydrogenation of ?-acyloxy-1-arylethanones.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-17-2013
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First hand: The first example of a palladium-catalyzed asymmetric hydrogenation of ?-acyloxy ketones (1) was accomplished to give the hydrogenated products 2 with by far the highest catalytic efficiency in up to quantitative conversions and excellent enantioselectivities. The hydrogenated products could serve as important intermediates for the preparation of many drug candidates. TFE=2,2,2-trifluoroethanol.
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Parkinsons disease-associated DJ-1 mutations increase abnormal phosphorylation of tau protein through Akt/GSK-3? pathways.
J. Mol. Neurosci.
PUBLISHED: 07-08-2013
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Hyperphosphorylated tau protein is the main component of neurofibrillary tangles found in Alzheimers disease and Parkinsons disease (PD). Mutations in DJ-1 have been identified as the causative gene for Parkinsons disease 7 (PARK7)-linked PD. DJ-1L166P and DJ-1D149A, two types of DJ-1 mutations, are most commonly studied as the loss-of-function mutations responsible for early-onset familial PD. Whether mutations in DJ-1 result in tauopathy is as yet unknown. In this study, we found that the L166P and D149A mutant isoforms of DJ-1 associated with familial PD cause tau phosphorylation at Ser202, Ser262, and PHF1 (396/404) sites in neuroblastoma 2a cells. Glycogen synthase kinase (GSK)-3? phosphorylation at serine 9 (Ser9) decreases around 50 % in DJ-1L166P- or DJ-1D149A-transfected cells, while there is no change in total levels of GSK-3?. Our results also indicate that overexpression of DJ-1L166P or DJ-1D149A leads to a significant decrease in the level of phosphorylation of Akt at Thr308, which plays a critical role in phosphorylating GSK-3? at Ser9 and inhibiting its kinase activity. Importantly, insulin, the activator for Akt, effectively attenuates the reduced phosphorylation level of GSK-3? at Ser9 induced by DJ-1L166P. Neither the expression of cyclin-dependent kinase 5 nor the level of PP2A activity was found to have changed, suggesting that the familial PD-associated DJ-1L166P and DJ-1D149A mutations increase tau phosphorylation by increasing the activity of GSK-3?. Finally, we found that administration of lithium chloride, a well-known GSK-3? inhibitor, resulted in decreased levels of phosphorylated tau in DJ-1L166P-transfected cells.
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Chemoselective transfer hydrogenation of ?,?-unsaturated ketones catalyzed by pincer-Pd complexes using alcohol as a hydrogen source.
Org. Lett.
PUBLISHED: 06-26-2013
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A pincer-Pd complex was utilized in the chemoselective transfer hydrogenation of ?,?-unsaturated ketones using n-BuOH as a hydrogen source and solvent. Good to excellent yields were obtained for various substrates even with reducible groups. Based on deuterium-labeling experiments, the reaction mechanism is proposed to occur via a pincer-Pd-hydride intermediate.
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Nras(G12D/+) promotes leukemogenesis by aberrantly regulating hematopoietic stem cell functions.
Blood
PUBLISHED: 05-17-2013
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Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (Nras(G12D/+)) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of Nras(G12D/+) in a pure C57BL/6 background does not induce hyperactivated granulocyte macrophage colony-stimulating factor signaling or increased proliferation in myeloid progenitors. It is thus unclear how Nras(G12D/+) signaling promotes leukemogenesis. Here, we show that hematopoietic stem cells (HSCs) expressing Nras(G12D/+) serve as MPN-initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant Nras(G12D/+) HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacologic and genetic approaches attenuates the cycling of Nras(G12D/+) HSCs and prevents the expansion of Nras(G12D/+) HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis.
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Notch1 gene mutations target KRAS G12D-expressing CD8+ cells and contribute to their leukemogenic transformation.
J. Biol. Chem.
PUBLISHED: 05-14-2013
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Acute T-cell lymphoblastic leukemia/lymphoma (T-ALL) is an aggressive hematopoietic malignancy affecting both children and adults. Previous studies of T-ALL mouse models induced by different genetic mutations have provided highly diverse results on the issues of T-cell leukemia/lymphoma-initiating cells (T-LICs) and potential mechanisms contributing to T-LIC transformation. Here, we show that oncogenic Kras (Kras G12D) expressed from its endogenous locus is a potent inducer of T-ALL even in a less sensitized BALB/c background. Notch1 mutations, including exon 34 mutations and recently characterized type 1 and 2 deletions, are detected in 100% of Kras G12D-induced T-ALL tumors. Although these mutations are not detected at the pre-leukemia stage, incremental up-regulation of NOTCH1 surface expression is observed at the pre-leukemia and leukemia stages. As secondary genetic hits in the Kras G12D model, Notch1 mutations target CD8(+) T-cells but not hematopoietic stem cells to further promote T-ALL progression. Pre-leukemia T-cells without detectable Notch1 mutations do not induce T-ALL in secondary recipient mice compared with T-ALL tumor cells with Notch1 mutations. We found huge variations in T-LIC frequency and immunophenotypes of cells enriched for T-LICs. Unlike Pten deficiency-induced T-ALL, oncogenic Kras-initiated T-ALL is not associated with up-regulation of the Wnt/?-catenin pathway. Our results suggest that up-regulation of NOTCH1 signaling, through either overexpression of surface NOTCH1 or acquired gain-of-function mutations, is involved in both T-ALL initiation and progression. Notch1 mutations and Kras G12D contribute cooperatively to leukemogenic transformation of normal T-cells.
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Asymmetric hydrogenation of ?-amino ketones with the bimetallic complex RuPHOX-Ru as the chiral catalyst.
Org. Biomol. Chem.
PUBLISHED: 05-10-2013
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Asymmetric hydrogenations of a series of ?-amino ketones were carried out with a bimetallic complex (RuPHOX-Ru) as the chiral catalyst. Almost all the reactions (performed in a mixed solvent system of toluene and H2O in the presence of KOH) gave quantitative conversions into their respective products with up to 99.9% ee. The RuPHOX-Ru catalyst is stable to both moisture and air. The procedure has the benefits of being inexpensive, environmentally friendly and highly efficient. Under a relatively low catalyst loading (TON = 2000), key intermediates of fluoxetine, tomoxetine and nisoxetine could be obtained in quantitative yield and in up to 99.9% ee. This methodology represents a promising alternative to the synthesis of the aforementioned drugs and their analogues.
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Therapeutic effect of sunitinib malate and its influence on blood glucose concentrations in a patient with metastatic insulinoma.
Expert Rev Anticancer Ther
PUBLISHED: 04-10-2013
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Standard cytotoxic chemotherapy has limited efficacy in advanced insulinomas, and control of blood glucose concentrations in these patients may be difficult. This article describes an elderly (74-year-old) man with metastatic insulinoma and severe hypoglycemia who was treated with repeated 6-week cycles of oral sunitinib malate (25 mg/day for 4 weeks, followed by 2 weeks off treatment). After treatment for more than 2 years, his condition improved and he continued to have a good quality of life with no evidence of tumor progression based on PET/CT findings. Although sunitinib treatment lowered the patients blood glucose concentrations further and induced repeated symptomatic hypoglycemic episodes, he was able to tolerate the treatment well after changing the timing of sunitinib dosing and adjusting his diet.
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Protective effects of memantine against methylmercury-induced glutamate dyshomeostasis and oxidative stress in rat cerebral cortex.
Neurotox Res
PUBLISHED: 03-05-2013
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Methylmercury (MeHg) is one of the ubiquitous environmental toxicant that leads to long-lasting neurological deficits in animals and humans. The identification of the underlying mechanisms has been a main focus of research in the neurotoxicology field. Glutamate (Glu) dyshomeostasis and oxidative stress have been identified as two critical mechanisms mediating MeHg-induced neurotoxicity. However, little has been known of the interaction between these two mechanisms that play in MeHg poisoning in vivo. We, therefore, developed a rat model of MeHg subchronic poisoning to evaluate its neurotoxic effects and investigated the neuroprotective role of memantine, a low-affinity, noncompetitive N-methyl-D-aspartate receptors (NMDARs) antagonist, against MeHg-induced neurotoxicity. Ninety rats were randomly divided into five groups: control, memantine control, MeHg-treated (4 and 12 ?mol/kg), and memantine pretreated. Administration of 12 ?mol/kg MeHg for 4 weeks significantly elevated total Hg levels, disrupted Glu metabolism, overexcited NMDARs, and led to intracellular calcium overload, which might be critical to excessive reactive oxygen species (ROS) formation in cerebral cortex. Meanwhile, MeHg administration reduced non-enzymatic (non-protein sulfhydryl, NPSH) and enzymatic (superoxide dismutase, SOD and glutathione peroxidase, GSH-Px) antioxidants; caused lipid, protein, and DNA oxidative damage; and enhanced neurocyte apoptosis in cerebral cortex. Moreover, glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) appear to be inhibited by MeHg exposure. Pretreatment with memantine at a dose of 5 ?mol/kg significantly prevented MeHg-induced alterations of Glu metabolism and oxidative stress, alleviated neurocyte apoptosis, and pathological injury. In conclusion, the results suggested that Glu dyshomeostasis and oxidative stress resulting from MeHg exposure contributed to neuronal injury. Memantine possesses the ability to attenuate MeHg-induced neurotoxicity through mechanisms involving its NMDARs-binding properties and indirect antioxidation.
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Hierarchical heterostructures of MnO? nanosheets or nanorods grown on Au-coated Co?O? porous nanowalls for high-performance pseudocapacitance.
Nanoscale
PUBLISHED: 03-02-2013
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The rational design and fabrication of more multi-component (material-combination) 3D hierarchical heterostructures for high-performance pseudocapacitor applications still remains a challenge. Herein, we have designed and synthesized a 3D hierarchical heterostructure of MnO2 nanosheets or nanorods grown on an Au-coated Co3O4 porous nanowall array, resembling a sandwich configuration of Co3O4@Au@MnO2, by a facial and controllable electrochemical deposition process. Due to their unique self-assembling architecture and characteristics including porous Co3O4 nanowalls, ultrathin MnO2 nanosheets, and a high conductivity Au layer sandwiched between them, each component provides a much-needed critical function for the efficient use of metal oxides for energy storage. The synthesized 3D hierarchical heterostructures exhibited favorable electrochemical performances, such as a high specific capacitances of 851.4 F g(-1) at 10 mV s(-1) and 1532.4 F g(-1) at 1 A g(-1), good rate performance and an excellent long-term cycling stability (almost no degradation after 5000 cycles), which are better than those of the reported Co3O4 or MnO2 based electrode materials, and thus could be considered as perspective materials for high-performance electrochemical capacitors.
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Effect of combined therapy of human Whartons jelly-derived mesenchymal stem cells from umbilical cord with sitagliptin in type 2 diabetic rats.
Endocrine
PUBLISHED: 02-06-2013
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Type 2 diabetes mellitus is the most common endocrine disease all over the world, while existing therapies can only ameliorate hyperglycemia or temporarily improve the response to insulin in target tissues, they cannot retard or improve the progressive ?-cell dysfunction persistently. Combined therapy of stem cells and sitagliptin might resolve this problem, we verified this hypothesis in a diabetic rat model. Except ten Wistar rats in normal control group, diabetic rats were divided into diabetic control group, WJ-MSCs group, sitagliptin group and WJ-MSCs + sitagliptin group and received homologous therapy. Ten weeks after therapy, diabetic symptoms, FPG and GHbA1c in WJ-MSCs group, sitagliptin group and WJ-MSCs + sitagliptin group were significantly less than those in diabetic control group (P < 0.05), while fasting C-peptide and number of ? cells in WJ-MSCs group and WJ-MSCs + sitagliptin group was significantly higher than those in diabetic control and sitagliptin group (P < 0.01). Glucagon and number of ? cells in sitagliptin group and WJ-MSCs + sitagliptin group were significantly lower than those in WJ-MSCs group and diabetic control group (P < 0.01). No symptoms of rejection and toxic effect were observed. Combined therapy of WJ-MSCs and sitagliptin can effectively ameliorate hyperglycemia, promote regeneration of islet ? cells and suppress generation of islet ? cells in diabetic rats, presenting a new therapy for type 2 diabetes although the exact mechanisms are unclear.
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Time course of current of injury is related to acute stability of active-fixation pacing leads in rabbits.
PLoS ONE
PUBLISHED: 01-24-2013
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Magnitude of current of injury (COI) consequent to pacemaker lead fixation is recognized as a predictor of acute lead stability. It is unclear whether dynamic monitoring of COI after lead fixation provides additional information beyond a single assessment performed at the time of fixation.
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Hypothermia induced by adenosine 5-monophosphate attenuates early stage injury in an acute gouty arthritis rat model.
Rheumatol. Int.
PUBLISHED: 01-15-2013
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To investigate whether the hypothermia induced by Adenosine 5-Monophosphate (5-AMP) could attenuate early stage injury in a rat acute gouty arthritis model. Ankle joint injection with monosodium urate monohydrate crystals (MSU crystals) in hypothermia rat model which was induced by 5-AMP and then observe whether hypothermia induced by 5-AMP could be effectively inhibit the inflammation on acute gouty arthritis in rats. AMP-induced hypothermia has protective effects on our acute gouty arthritis, which was demonstrated by the following criteria: (1) a significant reduction in the ankle swelling (p < 0.001); (2) a significant decrease in the occurrence of leukocyte infiltration and mild hemorrhage; (3) a significant reduction in the presence of serum Interleukin-1? (IL-1?, p < 0.001) and metalloproteinase-9 (MMP-9, p < 0.001); and (4) a significant inhibition in the Nuclear Factor -?appaB (NF-?B) activity (p < 0.001). AMP-induced hypothermia could inhibit acute inflammation reaction and protect the synovial tissue against acute injury in a rat acute gouty arthritis model.
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C-N bond cleavage of allylic amines via hydrogen bond activation with alcohol solvents in Pd-catalyzed allylic alkylation of carbonyl compounds.
J. Am. Chem. Soc.
PUBLISHED: 11-09-2011
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Hydrogen-bond-activated C-N bond cleavage of allylic amines was realized in Pd-catalyzed allylic alkylation to form the C-C bond product. The method could be expanded to a series of allylic amines and carbonyl compounds with excellent results. It provides a new and convenient access to C-C bond formation based on Pd-catalyzed allylic alkylation of allylic amines by using only inexpensive alcohol solvents.
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[Treatment of displaced radial head fractures with internal fixation].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 10-14-2011
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To analyse the procedure and effectiveness of internal fixation in treatment of displaced radial head fractures.
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Distinct requirements of hematopoietic stem cell activity and Nras G12D signaling in different cell types during leukemogenesis.
Cell Cycle
PUBLISHED: 09-01-2011
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We previously showed that widespread expression of Nras G12D/G12D from its endogenous locus in mice leads to an acute myeloproliferative disease (MPD) with a complete penetrance, whereas bone marrow-specific expression of Nras G12D/G12D in recipient mice did not result in sustained MPD phenotypes but 100% penetrant acute T-cell lymphoblastic leukemia/lymphoma (TALL). Such a phenotypic switch also is seen in the case of endogenous oncogenic Kras. Two possibilities might account for this observation and they are not necessarily mutually exclusive. First, the MPD phenotypes in primary Nras G12D/G12D mice might be a transient phenomenon attributable to microenvironmental factors that do not necessarily imply the potential for long-term maintenance in a hematopoietic-cell autonomous manner. Second, it is likely that MPD phenotypes are maintained by genetically altered hematopoietic stem cells (HSCs). Nras G12D/G12D signaling might substantially alter HSC behaviors (e.g. induce their proliferative exhaustion) so that these HSCs no longer sustain MPD phenotypes to a lethal stage in recipient mice. Here, we show some preliminary results to support the second hypothesis. Our results suggest that different lineages of hematopoietic cells might have differential requirements of HSC activity and Nras G12D signaling during leukemogenesis.
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Effects of lycopene and proanthocyanidins on hepatotoxicity induced by mercuric chloride in rats.
Biol Trace Elem Res
PUBLISHED: 08-15-2011
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To evaluate the protective potential of lycopene (Lyc) and proanthocyanidins (PCs) against mercuric chloride (HgCl(2))-induced hepatotoxicity, the study focused on the mechanism of oxidative stress. Firstly, the rats were subcutaneously (s.c.) injected with 0, 2.2, 4.4, and 8.8 ?mol/kg HgCl(2). Additionally, 40 mg/kg Lyc and 450 mg/kg PCs were given to the rats intragastrically (i.g.) before exposure to 8.8 ?mol/kg HgCl(2). Then, body weight, liver weight coefficient, mercury (Hg) contents, histological feature, ultrastructure, apoptosis, reactive oxygen species (ROS), glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver were measured. Lactate dehydrogenase (LDH) and alanine transaminase (ALT) in serum were determined. After exposure to different concentrations of HgCl(2), it was found that Hg contents, pathological and ultrastructure injury, activities of LDH and ALT, apoptosis, and levels of ROS, GSH, and MDA increased and the activities of SOD and GSH-Px decreased in a concentration-dependent manner. Further investigation found that pretreatment with Lyc and PCs inhibited ROS production, protected antioxidant enzymes, and reversed hepatotoxicity. We concluded that Lyc and PCs had hepatoprotective effects on HgCl(2)-induced toxicity by antagonizing oxidative stress in rat liver.
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Motivation and social contexts: a crossnational pilot study of achievement, power, and affiliation motives.
Int J Psychol
PUBLISHED: 07-26-2011
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Previous research suggests that there is a relationship between social contexts (e.g., economic growth, engagement in wars) and motives within populations. In particular, high achievement motive is associated with subsequent economic growth, which in turn increases power motive. Increased national achievement and power motives have been argued to precede social changes that lead to decreased affiliation motives, and engagement in wars. The present study aimed to examine differences in achievement, power, and affiliation motives between 266 college students in China (a nation with sustained high economic growth) and 255 college students in the USA (a nation with previously strong but now slowing economic growth, and engaged in war). Analysis of personal strivings suggested that Chinese college students showed significantly higher levels of achievement motive than the American college students, but American college students showed significantly higher levels of affiliation motive than Chinese college students. Overall, males exhibited higher achievement motivation than females. No significant interaction effects were found for gender by location for any of the three motives. The findings are discussed in relation to previous research.
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Effect of grape seed proanthocyanidin extracts on methylmercury-induced neurotoxicity in rats.
Biol Trace Elem Res
PUBLISHED: 06-29-2011
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As a highly toxic environmental pollutant, methylmercury (MeHg) can cause neurotoxicity in animals and humans. Considering the antioxidant property of grape seed proanthocyanidin extracts (GSPE), this study was aimed to evaluate the effect of GSPE on MeHg-induced neurotoxicity in rats. Rats were exposed to MeHg by intraperitoneal injection (4, 12 ?mol/kg, respectively) and GSPE was administered by gavage (250 mg/kg) 2 h later. After a 4-week treatment, phosphate-activated glutaminase, glutamine synthetase, glutathione peroxidase and superoxide dismutase activities, glutamate, glutamine, malondialdehyde and glutathione contents in cerebral cortex were measured. Reactive oxygen species (ROS) and apoptosis were also estimated in cells. The results showed that the MeHg-induced neurotoxicity was significantly attenuated. GSPE significantly decreased the production of ROS, counteracted oxidative damage and increased the antioxidants and antioxidant enzymes activities in rats prior to MeHg exposure. Moreover, the effects on the rate of apoptotic cells and the disturbance of glutamate homeostasis were correspondingly modulated. These observations highlighted the potential of GSPE in offering protection against MeHg-induced neurotoxicity.
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Large-scaled star-shaped ?-MnS nanocrystals with novel magnetic properties.
Chem. Commun. (Camb.)
PUBLISHED: 06-20-2011
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A cooperative thermal decomposition route to large-scaled star-shaped ?-MnS nanocrystals, which show novel magnetic properties, i.e., a high blocking temperature (275 K) and a large coercive field (1573 Oe), is reported.
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Endogenous oncogenic Nras mutation initiates hematopoietic malignancies in a dose- and cell type-dependent manner.
Blood
PUBLISHED: 05-17-2011
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Both monoallelic and biallelic oncogenic NRAS mutations are identified in human leukemias, suggesting a dose-dependent role of oncogenic NRAS in leukemogenesis. Here, we use a hypomorphic oncogenic Nras allele and a normal oncogenic Nras allele (Nras G12D(hypo) and Nras G12D, respectively) to create a gene dose gradient ranging from 25% to 200% of endogenous Nras G12D/+. Mice expressing Nras G12D(hypo)/G12D(hypo) develop normally and are tumor-free, whereas early embryonic expression of Nras G12D/+ is lethal. Somatic expression of Nras G12D/G12D but not Nras G12D/+ leads to hyperactivation of ERK, excessive proliferation of myeloid progenitors, and consequently an acute myeloproliferative disease. Using a bone marrow transplant model, we previously showed that ? 95% of animals receiving Nras G12D/+ bone marrow cells develop chronic myelomonocytic leukemia (CMML), while ? 8% of recipients develop acute T-cell lymphoblastic leukemia/lymphoma [TALL] (TALL-het). Here we demonstrate that 100% of recipients transplanted with Nras G12D/G12D bone marrow cells develop TALL (TALL-homo). Although both TALL-het and -homo tumors acquire Notch1 mutations and are sensitive to a ?-secretase inhibitor, endogenous Nras G12D/+ signaling promotes TALL through distinct genetic mechanism(s) from Nras G12D/G12D. Our data indicate that the tumor transformation potential of endogenous oncogenic Nras is both dose- and cell type-dependent.
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Meta-analysis of randomized controlled trials comparing isolated left ventricular and biventricular pacing in patients with chronic heart failure.
Am. J. Cardiol.
PUBLISHED: 04-28-2011
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Cardiac resynchronization therapy (CRT) has been mostly achieved by biventricular pacing (BVP) in patients with chronic heart failure (CHF), although it can also be provided by left ventricular pacing (LVP). The superiority of BVP over LVP remains uncertain. The present meta-analysis of randomized controlled trials was performed to compare the effects of LVP to BVP in patients with CHF. Outcomes analyzed included clinical status (6-minute walk distance, peak oxygen consumption, quality of life, New York Heart Association class), LV function (LV ejection fraction), and LV remodeling (LV end-systolic volume). Five trials fulfilled criteria for inclusion in analysis, which included 574 patients with CHF indicated for CRT. After a midterm follow-up, pooled analysis demonstrated that LVP resulted in similar improvements in 6-minute walk distance (weighted mean difference [WMD] 11.25, 95% confidence interval [CI] -12.39 to 34.90, p = 0.35), quality of life (WMD 0.34, 95% CI -3.72 to 4.39, p = 0.87), peak oxygen consumption (WMD 1.00, 95% CI -0.84 to 2.85, p = 0.29), and New York Heart Association class (WMD -0.19, 95% CI -0.79 to 0.42, p = 0.54). There was a trend toward a superiority of BVP over LVP for LV ejection fraction (WMD 1.28, 95% CI -0.11 to 2.68, p = 0.07) and LV end-systolic volume (WMD -5.73, 95% CI -11.86 to 0.39, p = 0.07). In conclusion, LVP achieves similar improvement in clinical status as BVP in patients with CHF, whereas there was a trend toward superiority of BVP over LVP for LV reverse modeling and systolic function.
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[Experimental study on culture method of human umbilical vein endothelial cells].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 03-25-2011
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To establish an efficient and stable culture method of human umbilical vein endothelial cells (HUVECs) in vitro so as to provide good source of seed cells for tissue engineered vascular grafts and for preclinical research.
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The protective effects of tea polyphenols and schisandrin B on nephrotoxicity of mercury.
Biol Trace Elem Res
PUBLISHED: 02-04-2011
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Mercury (Hg) is an occupational and environmental contaminant that is a well-recognized health hazard. To approach the concrete mechanisms of mercury nephrotoxicity and find out a new way to prevent it, the rats were subcutaneously injected with different dosages of mercuric chloride (HgCl(2))--0, 2.2, 4.4, and 8.8 ?mol/kg. The levels of Hg, blood urea nitrogen (BUN), urine protein, glutathione (GSH), malondialdehyde (MDA) and activities of N-acetyl-beta-D-glucosaminidase (NAG), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were investigated, and the levels of reactive oxygen species (ROS) and apoptosis and the pathological changes were also observed. In addition, the effects of 1 mmol/kg tea polyphenols (TP) and 0.04 mmol/kg schisandrin B (Sch B) were studied at 8.8 ?mol/kg HgCl(2). It was observed that the levels of Hg, BUN, urine protein, GSH, and MDA and activities of NAG, ALP, and LDH increased significantly; the activities of SOD and GSH-Px decreased significantly; the levels of ROS and apoptosis increased obviously; and many pathological changes occurred dose-dependently in the HgCl(2) injection groups. Further investigation indicated that pretreatment with TP and Sch B significantly reversed the toxic effects of HgCl(2). These results suggested that TP and Sch B might antagonize the nephrotoxicity caused by HgCl(2) exposure.
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Efficient palladium-catalyzed asymmetric allylic alkylation of ketones and aldehydes.
Org. Biomol. Chem.
PUBLISHED: 01-31-2011
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Palladium-catalyzed asymmetric allylic alkylation of ketones, via enamines generated in situ as nucleophiles, were carried out smoothly with chiral metallocene-based P,N-ligands. Under the same conditions, however, reactions of aldehydes could hardly be observed. Subsequently, this obstacle was resolved by using chiral metallocene-based P,P-ligands. Both ketones and aldehydes afforded excellent enantioselectivities with up to 98% ee and 94% ee, respectively.
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Prognostic significance of kappaB-Ras1 expression in gliomas.
Med. Oncol.
PUBLISHED: 01-17-2011
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Nuclear factor (NF)-kappa-B is a pleiotropic transcriptional regulator that plays important roles in cell differentiation, growth, tumorigenesis, and apoptosis. Constitutive NF-kappa-B is overexpressed and activated in various tumors, including gliomas. Here, we investigated the expression of NF-kappa-B inhibitor interacting ras-like protein 1 (?B-Ras1), which is one of the most important negative modulators of NF-kappa-B, and a well-known proliferation biomarker survivin protein. We performed immunohistochemistry and western blot analysis on 154 glioma specimens and 3 non-neoplastic brain parenchyma specimens. Immunohistochemistry showed a strong-to-weak range of ?B-Ras1 staining with increasing pathologic grade of glioma (P = 0.000). Immunoreactivity scores of ?B-Ras1 were 8.15 ± 0.72 in non-neoplastic brain parenchyma, 5.00 ± 0.29 in low-grade gliomas, 3.89 ± 0.30 in anaplasia astrocytomas, and 2.78 ± 0.25 in glioblastomas. In contrast, the immunoreactivity of survivin increased with pathological grade in gliomas. The immunohistochemical data were in line with the results from western blot analysis. Moreover, a non-parametric analysis revealed that the attenuated ?B-Ras1 expression was correlated with elevated survivin expression, large tumor diameter, frequent intra-tumor necrosis, and worse overall survival. These results indicated that ?B-Ras1 was down-regulated in gliomas compared to non-neoplastic brain parenchyma, and the expression was even lower in glioblastomas. In addition, multivariate analysis showed that ?B-Ras1 expression and intra-tumor necrosis were two important prognostic factors identified by the Cox proportional hazards model. Taken together, our study suggests that glioma patients with lower ?B-Ras1 expression have a worse prognosis, which is partly due to NF-kappa-B pathway-mediated aberrant proliferation of tumor cells.
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Characterization of two urostylid ciliates, Metaurostylopsis flavicana spec. nov. and Tunicothrix wilberti (Lin & Song, 2004) Xu et al., 2006 (Ciliophora, Stichotrichia), from a mangrove nature protection area in China.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 12-17-2010
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Two marine stichotrich ciliates, Metaurostylopsis flavicana spec. nov. and Tunicothrix wilberti (Lin & Song, 2004) Xu et al., 2006, isolated from the Shenzhen Mangrove Protection Area on the coast of the South China Sea, were investigated using live observation and protargol impregnation techniques. Metaurostylopsis flavicana is characterized by its elongate body shape, yellowish body colour and bright-yellow cortical granules that are either grouped around the cirri and the dorsal cilia or aligned between the rows of cirri and dorsal cilia. It has four to eight frontal, two frontoterminal, one buccal and seven to ten transverse cirri, a mid-ventral complex comprising 13-17 midventral cirral pairs in a row that extends about three-fifths of the body length, four left and three right marginal rows and three complete dorsal kineties. The small subunit rRNA gene of this species was sequenced and phylogenetic trees were constructed in which M. flavicana does not group with its congeners, suggesting that the genus Metaurostylopsis is paraphyletic. Some supplementary morphological and morphogenetic traits for Tunicothrix wilberti are also documented.
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Carbon nanotubes as field emitter.
J Nanosci Nanotechnol
PUBLISHED: 12-03-2010
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Carbon nanotubes (CNTs) have recently emerged as a promising material of electron field emitters. They exhibit extraordinary field emission properties because of their high electrical conductivity, high aspect ratio "needle like" shape for optimum geometrical field enhancement, and remarkable thermal stability. In this Review, we emphasize the estimation and influencing factors of CNTs emission properties, and discuss in detail the emission properties of macroscopic CNT cathodes, especially fabricated by transplant methods, and describe recent progress on understanding of CNT field emitters and analyze issues related to applications of CNT based cold cathodes in field emission display (FED). We foresee that CNT-FED will take an important place in display technologies in the near future.
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Oriented free-standing ammonium vanadium oxide nanobelt membranes: highly selective absorbent materials.
Chemistry
PUBLISHED: 11-26-2010
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Highly selective, absorbent, free-standing, paper-like membranes made of ammonium vanadium oxide (NH(4)V(4)O(14)) nanobelts have been engineered by taking advantage of the nanoscaled self-assembly of architectures that display a mesh structure with an average periodic pore size of about 5 to 10?nm. The NH(4)V(4)O(14) nanobelts are synthesized by using a simple hydrothermal process, and exhibit the same orientation and assemble into bundles, each about 40 to 80?nm in width, 3 to 5?nm in thickness, and up to several millimeters in length. Importantly, the as-obtained NH(4)V(4)O(14) nanobelt membranes can highly selectively absorb a variety of organic solvents, covering both polar and non-polar solvents, for example, the absorbent capacity of glycol is 28 times as high as the initial weight of the membrane, and it can even separate organic solvents with similar polarities and absorb solid contaminants in organic solvents. These highly selective, absorbent membrane materials can be an ideal candidate for the separation and removal of pollution in industrial and environmental applications.
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Endogenous oncogenic Nras mutation promotes aberrant GM-CSF signaling in granulocytic/monocytic precursors in a murine model of chronic myelomonocytic leukemia.
Blood
PUBLISHED: 10-04-2010
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Oncogenic NRAS mutations are frequently identified in myeloid diseases involving monocyte lineage. However, its role in the genesis of these diseases remains elusive. We report a mouse bone marrow transplantation model harboring an oncogenic G12D mutation in the Nras locus. Approximately 95% of recipient mice develop a myeloproliferative disease resembling the myeloproliferative variant of chronic myelomonocytic leukemia (CMML), with a prolonged latency and acquisition of multiple genetic alterations, including uniparental disomy of oncogenic Nras allele. Based on single-cell profiling of phospho-proteins, a novel population of CMML cells is identified to display aberrant granulocyte-macrophage colony stimulating factor (GM-CSF) signaling in both the extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription 5 (Stat5) pathways. This abnormal signaling is acquired during CMML development. Further study suggests that aberrant Ras/ERK signaling leads to expansion of granulocytic/monocytic precursors, which are highly responsive to GM-CSF. Hyperactivation of Stat5 in CMML cells is mainly through expansion of these precursors rather than up-regulation of surface expression of GM-CSF receptors. Our results provide insights into the aberrant cytokine signaling in oncogenic NRAS-associated myeloid diseases.
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Morphological studies on two marine colepid ciliates from Qingdao, China, Nolandia orientalis spec. nov. and Pinacocoleps similis (Kahl, 1933) comb. nov. (Ciliophora, Colepidae).
Eur. J. Protistol.
PUBLISHED: 09-15-2010
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Recent studies have revealed that the "lower" marine ciliates are far more diverse than previously suspected. During a survey on the ciliate fauna in coastal waters of Qingdao, northern China, we have isolated about 30 new or poorly known taxa. In the present study two colepid species are investigated, Nolandia orientalis spec. nov. and Pinacocoleps similis (Kahl, 1933) comb. nov. (basionym: Coleps similis Kahl, 1933). Their morphology and infraciliature are documented based on living observations and silver impregnations. The new species Nolandia orientalis differs from the type species N. nolandi mainly in the structure of tier plates. The structure of the tier plates was also the basis for transferring Coleps similis Kahl, 1933 to the genus Pinacocoleps and for three further new combinations: Pinacocoleps heteracanthus (Noland, 1937) comb. nov. (basionym: Coleps heteracanthus Noland, 1937), P. spiralis (Noland, 1937) comb. nov. (basionym Coleps spiralis Noland, 1937) and Pinacocoleps arenarius (Bock, 1952) comb. nov. (basionym: Coleps arenarius Bock, 1952).
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Methane emissions from a full-scale A/A/O wastewater treatment plant.
Bioresour. Technol.
PUBLISHED: 07-31-2010
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Methane (CH(4)) emissions from a full-scale anaerobic/anoxic/oxic (A/A/O) wastewater treatment plant (WWTP) (Jinan, China) were investigated during spring and summer of 2010. Results showed that the major emission sources of CH(4) performed the following descending order: anaerobic tanks, oxic tanks, aerated grit chambers and sludge concentration tanks. The total annual fluxes of CH(4) emissions from the Jinan WWTP were 1.69 × 10(4)kg yr(-1), with the emission factors of per capita emissions of 11.3g CH(4) person(-1)yr(-1) and flow-based emissions of 1.55 × 10(-4)g CH(4) (L of wastewater)(-1). The estimated source strength of methane for all WWTPs in China was 6.2 Gg yr(-1) (1 Gg=10(9)g). The most significant factors influencing methane emissions were dissolved oxygen concentration in aerated grit chamber and oxic tank and water temperature in high density settler tanks.
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A potential new method for determination of the fluence (UV dose) delivered in UV reactors involving the photodegradation of free chlorine.
Water Environ. Res.
PUBLISHED: 05-04-2010
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In the operation of UV reactors, an important step is to validate if the UV reactor can deliver the design fluence (UV dose) to achieve the required disinfection credit. Free chlorine is used widely in water and wastewater treatment and often is found in the water passing through a UV reactor. Free chlorine is degraded when passing through a UV reactor. This study investigates the potential application of the photodegradation of free chlorine (PFC) to determine the fluence (UV dose) delivered in UV reactors. Using a bench-scale UV reactor, the PFC was investigated at difference UV doses, which also were measured by a biodosimetry method. The results obtained here show that the PFC method has a high correlation with the delivered UV dose (as estimated from the biodosimetry measurements) and is independent of operating conditions, such as flowrate and UV transmittance. In addition, this study indicates that only chloride and chlorate are generated when free chlorine is photodegraded.
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Highly efficient ultraviolet photodetectors based on TiO(2) nanocrystal-polymer composites via wet processing.
Nanotechnology
PUBLISHED: 04-14-2010
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Solution-processed inorganic/organic hybrid films based on anatase TiO(2) nanocrystals and poly (9,9-dihexylfluorene) (PFH) are fabricated via a simple spin-coating method and characterized by atomic force microscopy, UV-vis absorption and photoluminescence spectra. The photodetector devices are made from hybrid TiO(2)/PFH bulk heterojunction films sandwiched between poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) pre-coated ITO and Al electrodes. The device characteristics, including current-voltage (I-V) curves under UV illumination, spectral response, response time and bias dependence, are studied. The photovoltaic effect is observed and the photocurrent shows an increase with increasing TiO(2) content from 2.5 to 11 wt%. The high UV photo-to-dark current ratio of 10(3), fast response time less than 200 ms and a responsivity of 54.6 mA W( - 1) are obtained for the hybrid photodetector. The fast photoresponse is attributed to the enhanced interfacial dissociation of excitons. The overlap of the spectral response with the UV-A range (320-400 nm) and the low-cost wet fabrication method show their potential for environmental and biological uses.
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A new one-dimensional radiative equilibrium model for investigating atmospheric radiation entropy flux.
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
PUBLISHED: 04-07-2010
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A new one-dimensional radiative equilibrium model is built to analytically evaluate the vertical profile of the Earths atmospheric radiation entropy flux under the assumption that atmospheric longwave radiation emission behaves as a greybody and shortwave radiation as a diluted blackbody. Results show that both the atmospheric shortwave and net longwave radiation entropy fluxes increase with altitude, and the latter is about one order in magnitude greater than the former. The vertical profile of the atmospheric net radiation entropy flux follows approximately that of the atmospheric net longwave radiation entropy flux. Sensitivity study further reveals that a darker atmosphere with a larger overall atmospheric longwave optical depth exhibits a smaller net radiation entropy flux at all altitudes, suggesting an intrinsic connection between the atmospheric net radiation entropy flux and the overall atmospheric longwave optical depth. These results indicate that the overall strength of the atmospheric irreversible processes at all altitudes as determined by the corresponding atmospheric net entropy flux is closely related to the amount of greenhouse gases in the atmosphere.
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Enzymatic hydrolysis of Alaska pollack (Theragra chalcogramma) skin and antioxidant activity of the resulting hydrolysate.
J. Sci. Food Agric.
PUBLISHED: 04-01-2010
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Fish skin, a by-product of the food industry, contains a large amount of collagen. However, only a small proportion of fish skin is used in the production of leather materials and animal feedstuffs, most of it being discarded. The aims of this study were to prepare peptides from Alaska pollack (Theragra chalcogramma) skin by enzymatic hydrolysis and to evaluate the antioxidant activity of the resulting hydrolysate.
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Body dissatisfaction, engagement in body change behaviors and sociocultural influences on body image among Chinese adolescents.
Body Image
PUBLISHED: 01-20-2010
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Body dissatisfaction and body image disorders are becoming increasingly prevalent in developing non-Western countries such as China, but there is a lack of research examining the sociocultural factors that in other contexts have been associated with these problems. The current study investigated body dissatisfaction, engagement in body change behaviors, and sociocultural pressures on body image, and the relationships between these variables among 517 adolescent males (N=219) and females (N=298) in China. Females reported greater body dissatisfaction than males, and males reported using strategies to increase their muscle bulk more often than females. Males reported pressure from a variety of sociocultural sources to increase their muscles or weight, while females reported pressure from the media to lose weight. For males body dissatisfaction was predicted by pressure from peers to increase their muscle bulk, while for females pressure to lose weight from peers, adult relatives, and the media was likely to increase body dissatisfaction. Pressure from the media and adult relatives was also predictive of body change behaviors in both males and females. The findings are discussed in relation to previous research in both Western and non-Western contexts.
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Is right ventricular outflow tract pacing superior to right ventricular apex pacing in patients with normal cardiac function?
Clin Cardiol
PUBLISHED: 12-23-2009
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Whether right ventricular outflow tract (RVOT) pacing is superior to right ventricular apex (RVA) pacing in terms of ventricular synchrony, cardiac function, and remodeling in patients with normal cardiac function is still unknown.
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