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Find video protocols related to scientific articles indexed in Pubmed.
Molecular insight into nanoscale water films dewetting on modified silica surfaces.
Phys Chem Chem Phys
PUBLISHED: 11-20-2014
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In this work, molecular dynamics simulations are adopted to investigate the microscopic dewetting mechanism of nanoscale water films on methylated silica surfaces. The simulation results show that the dewetting process is divided into two stages: the appearance of dry patches and the quick contraction of the water film. First, the appearance of dry patches is due to the fluctuation in the film thickness originating from capillary wave instability. Second, for the fast contraction of water film, the unsaturated electrostatic and hydrogen bond interactions among water molecules are the driving forces, which induce the quick contraction of the water film. Finally, the effect of film thickness on water films dewetting is studied. Research results suggest that upon increasing the water film thickness from 6 to 8 Å, the final dewetting patterns experience separate droplets and striation-shaped structures, respectively. But upon further increasing the water film thickness, the water film is stable and there are no dry patches. The microscopic dewetting behaviors of water films on methylated silica surfaces discussed here are helpful in understanding many phenomena in scientific and industrial processes better.
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DNA photocleavage in anaerobic conditions by a Ru(ii) complex: a new mechanism.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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[Ru(bpy)2(py-SO3)](+) (bpy = 2,2'-bipyridine and py-SO3 = pyridine-2-sulfonate) was found to undergo py-SO3 dissociation upon visible light irradiation (?470 nm) via Ru-O homolysis, producing reactive free radical species, and is thus able to not only photobind but also photocleave DNA in hypoxic conditions.
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Molecular Insights into How Ligands Activate or Inactivate LasR.
Chem. Biol.
PUBLISHED: 11-07-2014
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The article by Gerdt and colleagues in this issue of Chemistry & Biology provides molecular insights into how nonlactone quorum sensing modulators either activate or deactivate LasR. Interestingly, an antagonist could flip into an agaonist upon mutation of a single residue in the autoinducer binding site.
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Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice.
J. Pineal Res.
PUBLISHED: 11-05-2014
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Silent information regulator 1 (SIRT1), a type of histone deacetylase, is a highly effective therapeutic target for protection against ischemia reperfusion (IR) injury (IRI). Previous studies showed that melatonin preserves SIRT1 expression in neuronal cells of newborn rats after hypoxia-ischemia. However, the definite role of SIRT1 in the protective effect of melatonin against cerebral IRI in adult has not been explored. In this study, the brain of adult mice were subjected to IRI. Prior to this procedure, the mice were given intraperitoneal with or without the SIRT1 inhibitor, EX527. Melatonin conferred a cerebralprotective effect, as shown by reduced infarct volume, lowered brain edema and increased neurological scores. The melatonin-induced up-regulation of SIRT1 was also associated with an increase in the anti-apoptotic factor, Bcl2, and a reduction in the pro-apoptotic factor Bax. Moreover, melatonin resulted in a well-preserved mitochondrial membrane potential (MMP), mitochondria Complex I activity, mitochondrial cytochrome c level while it reduced cytosolic cytochrome c level. However, the melatonin-elevated mitochondrial function was reversed by EX527 treatment. In summary, our results demonstrate that melatonin treatment attenuates cerebral IRI by reducing IR-induced mitochondrial dysfunction through the activation of SIRT1 signaling. This article is protected by copyright. All rights reserved.
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Response of alpine grassland to elevated nitrogen deposition and water supply in China.
Oecologia
PUBLISHED: 10-14-2014
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Species composition and productivity are influenced by water and N availability in semi-arid grasslands. To assess the effects of increased N deposition and water supply on plant species composition and productivity, two field experiments with four N addition treatments, and three N and water combination treatments were conducted in alpine grassland in the mid Tianshan mountains, northwest China. When considering N addition alone, aboveground biomass (AGB) of forbs (FAGB) responded less to N addition than AGB of grasses (GAGB). GAGB increased as an effect of N combined with water addition but FAGB did not show such an effect, reflecting a stronger response of grasses to the interaction of water availability and N than forbs. Under all treatments, N allocation to the aboveground tissue did not change for either forbs or grasses. N deposition and water addition did not alter species richness in the present study. These results suggest that N addition generally promoted AGB but had little effect on species richness in wet years. Snowfall in winter combined with rainfall in the early growing season likely plays a critical role in regulating plant growth of the subsequent year in the alpine grassland.
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Antidiabetic Effect of Schisandrae Chinensis Fructus Involves Inhibition of the Sodium Glucose Cotransporter.
Drug Dev. Res.
PUBLISHED: 10-10-2014
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Preclinical Research Schisandrae Chinensis Fructus (SCF), the fruit of Schisandra chinensis (Turcz.) Baill. (family Schisandraceae) is traditionally used as a tonic and antidiabetic agent in Asia. In this study, SCF was investigated for its effects on sodium glucose cotransporters 1 and 2 (SGLT 1 and 2) expressed in a COS-7 cell line for its specificity in inhibiting SGLT2, which is a novel mechanism to screen for potential antidiabetic agents. Using a bioassay-guided fractionation, we then tried to isolate and identify the active fraction(s)/component(s). The ethanol extract of SCF at a concentration of 1?mg/mL significantly inhibited 89% of SGLT1 and 73% of SGLT2 activities in a [(14) C]-?-methyl-d-glucopyranoside ([(14) C]-AMG) uptake assay. Fractionation of the ethanol extract yielded nine fractions, of which F8, at a concentration of 1?mg/mL, was specific in inhibiting SGLT 2 (42% inhibition, P?
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[Inorganic N deposition in the Bayinbuluk alpine grassland of the central Tianshan mountains].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 09-17-2014
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N deposition has increased significantly with economic development and intensive human activities in China and has affected natural ecosystems in remote areas. To evaluate the atmospheric N deposition of the Bayinbuluk alpine grassland of the central Tianshan Mountains, the dry and wet N depositions were monitored from May 2010 to December 2011. Fluxes of HNO3, NH3, NO2, particulate ammonium and nitrate (pNH4+ and pNO3-) averaged at 1.47, 0.68, 0.13, 0.23 and 0.25 kg N x hm(-2) x a(-1), respectively. Wet depositions of NH(4+)-N and NO(3-)-N were 2.47 and 1.59 kg N x hm(-2) x a(-1), respectively. Total atmospheric inorganic N deposition fluxes averaged at 6.82 kg N x hm(-2) x a(-1), and the wet and dry depositions were 4.06 and 2.76 kg N x hm(-2) x a(-1), respectively. Nitrogen deposition fluxes showed a significant seasonal change, with 72.1% of dry N deposition occurring in spring and summer, and 78.3% of wet N deposition concentrating in summer and autumn.
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Response of uptake and translocation of phenanthrene to nitrogen form in lettuce and wheat seedlings.
Environ Sci Pollut Res Int
PUBLISHED: 09-10-2014
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Polycyclic aromatic hydrocarbons (PAHs) are widespread chemicals that are potentially carcinogenic and toxic to human due to dietary intake of food crops contaminated by PAHs. To date, the mechanisms underlying root uptake and acropetal translocation of PAHs in crops are poorly understood. Here we describe uptake and translocation of phenanthrene (a model PAH) in relation to nitrogen form and concentration in wheat and lettuce seedlings. At concentrations of 0-15 mM, phenanthrene uptake by roots is enhanced with an increase in ammonium and inhibited with an increment of nitrate. Phenanthrene concentration in shoots is much lower than in roots, suggesting that the direction of phenanthrene transport is acropetal. Ammonium reduces both phenanthrene accumulation and bioconcentration factor in shoots, as well as translocation factor, but nitrate elevates them. Phenanthrene uptake increases nutrient solution pH in the treatments with either nitrate or ammonium. Thus, it is concluded that the root uptake and acropetal translocation of phenanthrene in crops are associated with nitrogen form. Our results provide both a novel insight into the mechanism on PAH transport in higher plants and a promising agronomic strategy to minimize PAH contamination in crops or to improve phytoremediation of PAH-contaminated soils or water via nitrogen management.
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MicroRNA-22 Induces Endothelial Progenitor Cell Senescence by Targeting AKT3.
Cell. Physiol. Biochem.
PUBLISHED: 09-01-2014
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Objectives: Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization. The number and function of EPCs declines as part of aging-associated senescence, thereby potentially contributing to vascular pathologies. Here, we investigated the significance and molecular mechanisms of microRNA-22 (miR-22) governing EPC senescence. Methods: EPCs were isolated from human circulating mononuclear cells from healthy young and aged volunteers. Cell senescence, proliferation, migration and tube formation ability were detected by SA-?-gal staining assay, MTT assay, transwell assay and Matrigel-based angiogenesis assay. Gene and protein expression were analyzed by qRT-PCR and Western blot respectively. Results: We found that miR-22 was upregulated in aged EPCs. Overexpression of miR-22 in young EPCs induced cell senescence, decreased proliferation and migration, and impaired angiogenesis in vitro. Conversely, silencing of endogenous miR-22 led to decreased cell senescence, increased proliferation and migration, and improved angiogenesis. AKT3 was identified as a direct target of miR-22, and restoration of AKT3 expression attenuated the effects of miR-22 in young EPCs. Conclusion: Our results indicate that miR-22 induces EPC senescence by downregulating AKT3 expression, providing a potential novel target for the reversal of EPC dysfunction in angiogenesis. © 2014 S. Karger AG, Basel.
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Bacterial Community Structure of Autotrophic Denitrification Biocathode by 454 Pyrosequencing of the 16S rRNA Gene.
Microb. Ecol.
PUBLISHED: 09-01-2014
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Few studies have been conducted to explore the community composition in denitrifying biocathode. Herein, the microbial communities of denitrifying biocathodes yielding current of 1 mA (reactor C1) and 1.5 mA (reactor C2) were characterized by 454 pyrosequencing. The nitrate removal efficiencies in C1 and C2 were about 93 and 85 %, respectively. The optimization of data generated high-quality sequences of 18509 in C1 and 14857 in C2. Proteobacteria was the predominant phylum, and Bacteroidetes, Chloroflexi, and Planctomycetes were the subdominant groups. Classes of Alphaproteobacteria, Anaerolineae, and Phycisphaerae may benefit the performance of current production and nitrate removal. Twenty-nine dominant operational taxonomic units (OTUs) accounted for 64 and 65 % of sequences in C1 and C2, respectively. A denitrifying pathway was constructed based on the phylogenetic analysis and function inferring of the dominant OTUs. Obviously, the 454 pyrosequencing provided a high-resolution profile of bacteria community in denitrifying biocathode.
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SeMet Mediates Anti-inflammation in LPS-Induced U937 Cells Targeting NF-?B Signaling Pathway.
Inflammation
PUBLISHED: 08-22-2014
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In previous studies, selenium (Se) was reported to play critical roles in anti-inflammatory activities. Nevertheless, limited information could be obtained during inflammation about selenomethionine (SeMet) in U937 human macrophage cells. The purpose of this study was to investigate the effects of SeMet on the inflammatory responses to lipopolysaccharide (LPS)-induced U937 macrophage cells and the signaling pathways targeted. U937 cells were pretreated with SeMet (1 ?M) and subsequently induced with LPS (1 ?g/ml) for 24 h. In the cell counting kit-8 assay (CCK-8), SeMet significantly inhibits the proliferation of U937 cells. SeMet also inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) stimulated by LPS. In the Western blot assay and real-time polymerase chain reaction (RT-PCR), SeMet significantly reduced protein expression and production of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-?), and COX-2 in U937 cells. Furthermore, SeMet markedly suppressed the LPS-mediated activation of nuclear factor-kappa B (NF-?B) by blocking the degradation of inhibitor-?B proteins (I?B?) and lessening the translocations of P50 subunit content of NF-?B in the nucleus. These findings suggested the anti-inflammatory activity of SeMet in U937 cells; indicating that SeMet might be a potential treatment for inflammation therapy.
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Association of CVD candidate gene polymorphisms with ischemic stroke and cerebral hemorrhage in Chinese individuals.
PLoS ONE
PUBLISHED: 08-21-2014
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Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.
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Identification of bromophenol thiohydantoin as an inhibitor of DisA, a c-di-AMP synthase, from a 1000 compound library, using the coralyne assay.
Chem. Commun. (Camb.)
PUBLISHED: 08-14-2014
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c-di-AMP is an important bacterial second messenger found in Gram-positive and mycobacteria. c-di-AMP regulates myriads of processes in bacteria as well as immune response in higher organisms so interest in small molecules that would attenuate the activity of c-di-AMP metabolism enzymes is high. Herein, we report the first small molecule inhibitor of a c-di-AMP synthase, DisA, using a coralyne-based assay.
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Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer.
Cancer Med
PUBLISHED: 08-13-2014
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Poly (ADP) ribose polymerase (PARP) plays a key role in DNA repair and is highly expressed in small cell lung cancer (SCLC). We investigated the therapeutic impact of PARP inhibition in SCLC. In vitro cytotoxicity of veliparib, cisplatin, carboplatin, and etoposide singly and combined was determined by MTS in 9 SCLC cell lines (H69, H128, H146, H526, H187, H209, DMS53, DMS153, and DMS114). Subcutaneous xenografts in athymic nu/nu mice of H146 and H128 cells with relatively high and low platinum sensitivity, respectively, were employed for in vivo testing. Mechanisms of differential sensitivity of SCLC cell lines to PARP inhibition were investigated by comparing protein and gene expression profiles of the platinum sensitive and the less sensitive cell lines. Veliparib showed limited single-agent cytotoxicity but selectively potentiated (?50% reduction in IC50 ) cisplatin, carboplatin, and etoposide in vitro in five of nine SCLC cell lines. Veliparib with cisplatin or etoposide or with both cisplatin and etoposide showed greater delay in tumor growth than chemotherapy alone in H146 but not H128 xenografts. The potentiating effect of veliparib was associated with in vitro cell line sensitivity to cisplatin (CC = 0.672; P = 0.048) and DNA-PKcs protein modulation. Gene expression profiling identified differential expression of a 5-gene panel (GLS, UBEC2, HACL1, MSI2, and LOC100129585) in cell lines with relatively greater sensitivity to platinum and veliparib combination. Veliparib potentiates standard cytotoxic agents against SCLC in a cell-specific manner. This potentiation correlates with platinum sensitivity, DNA-PKcs expression and a 5-gene expression profile.
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A novel single-side azobenzene-grafted Anderson-type polyoxometalate for recognition-induced chiral migration.
Chem. Commun. (Camb.)
PUBLISHED: 08-05-2014
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A three-component supramolecular hybrid system based on host-guest recognition and electrostatic interaction has been developed for a consecutive chiral transfer from an alpha-cyclodextrin to cationic dyes via the bridge of a new azobenzene-grafted Anderson-type polyoxometalate cluster.
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Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.
ACS Appl Mater Interfaces
PUBLISHED: 07-30-2014
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Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration.
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Differential expression and regulation of Ido2 in the mouse uterus during peri-implantation period.
In Vitro Cell. Dev. Biol. Anim.
PUBLISHED: 07-22-2014
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Ido2 is involved in tryptophan catabolism and immunity, but its physiological functions remain poorly understood. This study was undertaken to examine the expression and regulation of Ido2 gene in mouse uterus during the peri-implantation period. The results showed that Ido2 mRNA was highly expressed on day 4 of pregnancy and in the delayed implantation uterus. On days 5-8 of pregnancy, a low level of Ido2 expression was observed in the uteri. Simultaneously, Ido2 mRNA was also lowly expressed in the decidualized uterus. In the uterine stromal cells, 8-Br-cAMP could inhibit the expression of Ido2 mRNA. Moreover, Ido2 mRNA expression was gradually decreased after the stromal cells were treated with estrogen and progesterone and reached a nadir at 96 h. Further study found that overexpression of Ido2 could downregulate the expression of decidualization marker genes PRL, IGFBP1, and Dtprp under in vitro decidualization, while inhibition of Ido2 with devo-1-methyl-tryptophan (D-1-MT) could upregulate the expression of these marker genes. Under in vitro decidualization, overexpression of Ido2 could suppress the proliferation of uterine stromal cells and elevate the expression of Bax and MMP2 genes. On the contrary, Ido2 inhibitor D-1-MT could enhance the proliferation of stromal cells and expression of Bcl2 gene but decline the Bax/Bcl2 ratio. In the uterine stromal cells, estrogen and progesterone could induce the expression of Ido2 mRNA. These data indicate that Ido2 may be important for mouse embryo implantation and decidualization.
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InCl3-catalyzed conversion of carbohydrates into 5-hydroxymethylfurfural in biphasic system.
Bioresour. Technol.
PUBLISHED: 07-20-2014
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InCl3, a water-compatible Lewis acid, was used for the conversion of microcrystalline cellulose to produce 5-hydroxymethylfurfural (HMF) in a H2O/THF biphasic system. Addition of NaCl increased the HMF yield significantly but suppressed the levulinic acid (LA) formation. The HMF yield of 39.7% was obtained in 2h at 200°C in the NaCl-H2O/THF catalytic system catalyzed by InCl3. The catalytic system also showed effectiveness to convert other carbohydrates to HMF, including glucose, fructose, sucrose, starch, which demonstrated great potential towards different feedstocks.
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Salinity tolerance in soybean is modulated by natural variation in GmSALT3.
Plant J.
PUBLISHED: 07-18-2014
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The identification of genes that improve the salt tolerance of crops is essential for the effective utilization of saline soils for agriculture. Here, we use fine mapping in a soybean (Glycine max (L.) Merr.) population derived from the commercial cultivars Tiefeng 8 and 85-140 to identify GmSALT3 (salt tolerance-associated gene on chromosome 3), a dominant gene associated with limiting the accumulation of sodium ions (Na(+) ) in shoots and a substantial enhancement in salt tolerance in soybean. GmSALT3 encodes a protein from the cation/H(+) exchanger family that we localized to the endoplasmic reticulum and which is preferentially expressed in the salt-tolerant parent Tiefeng 8 within root cells associated with phloem and xylem. We identified in the salt-sensitive parent, 85-140, a 3.78-kb copia retrotransposon insertion in exon 3 of Gmsalt3 that truncates the transcript. By sequencing 31 soybean landraces and 22 wild soybean (Glycine soja) a total of nine haplotypes including two salt-tolerant haplotypes and seven salt-sensitive haplotypes were identified. By analysing the distribution of haplotypes among 172 Chinese soybean landraces and 57 wild soybean we found that haplotype 1 (H1, found in Tiefeng 8) was strongly associated with salt tolerance and is likely to be the ancestral allele. Alleles H2-H6, H8 and H9, which do not confer salinity tolerance, were acquired more recently. H1, unlike other alleles, has a wide geographical range including saline areas, which indicates it is maintained when required but its potent stress tolerance can be lost during natural selection and domestication. GmSALT3 is a gene associated with salt tolerance with great potential for soybean improvement.
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Streptomyces vulcanius sp. nov., a novel actinomycete isolated from volcanic sediment.
Antonie Van Leeuwenhoek
PUBLISHED: 07-09-2014
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A novel actinomycete, designated strain NEAU-C3(T), was isolated from volcanic sediment collected from Longwan, Jilin province, north China and characterized using a polyphasic approach. The organism was found to have morphological and chemotaxonomic characteristics typical of the members of the genus Streptomyces. EzTaxon-e analysis of the 16S rRNA gene sequence indicated strain NEAU-C3(T) to be most closely related to Streptomyces hygroscopicus subsp. ossamyceticus JCM 4965(T) (97.7 % sequence similarity) and Streptomyces torulosus JCM 4872(T) (97.7 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-C3(T) belongs within the genus Streptomyces and forms a separate subclade, an association that was supported by a bootstrap value of 72 % in the neighbour-joining tree and also recovered with the maximum-likelihood algorithm. The DNA-DNA hybridization values between strain NEAU-C3(T) and the two most closely related type strains were low enough to justify the assignment of the strain to a novel species. On the basis of these phenotypic, phylogenetic and chemotaxonomic characteristics, it is concluded that strain NEAU-C3(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces vulcanius sp. nov. is proposed. The type strain is NEAU-C3(T) (=CGMCC 4.7177(T)=DSM 42139(T)).
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Oil accumulation mechanisms of the oleaginous microalga Chlorella protothecoides revealed through its genome, transcriptomes, and proteomes.
BMC Genomics
PUBLISHED: 07-01-2014
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Microalgae-derived biodiesel is a promising substitute for conventional fossil fuels. In particular, the green alga Chlorella protothecoides sp. 0710 is regarded as one of the best candidates for commercial manufacture of microalgae-derived biofuel. This is due not only to its ability to live autotrophically through photosynthesis, but also to its capacity to produce a large amount of biomass and lipid through fermentation of glucose. However, until the present study, neither its genome sequence nor the platform required for molecular manipulations were available.
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A solution-phase bifunctional catalyst for lithium-oxygen batteries.
J. Am. Chem. Soc.
PUBLISHED: 06-12-2014
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A lithium-oxygen battery would deliver the highest energy density of a rechargeable battery, but the multiphase electrochemical reaction on the air cathode has difficulty proceeding when operated with only solid catalysts. We report here the organic-electrolyte-dissolved iron phthalocyanine (FePc) as a shuttle of (O2)(-) species and electrons between the surface of the electronic conductor and the insulator Li2O2 product of discharge. The Li2O2 is observed to grow and decompose without direct contact with carbon, which greatly enhances the electrochemical performance. Our results signal that the use of molecular shuttles that are catalytically active may prove to be enablers of a practical lithium-air rechargeable battery.
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Molecular-scale Hydrophilicity Induced by Solute: Molecular-thick Charged Pancakes of Aqueous Salt Solution on Hydrophobic Carbon-based Surfaces.
Sci Rep
PUBLISHED: 06-10-2014
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We directly observed molecular-thick aqueous salt-solution pancakes on a hydrophobic graphite surface under ambient conditions employing atomic force microscopy. This observation indicates the unexpected molecular-scale hydrophilicity of the salt solution on graphite surfaces, which is different from the macroscopic wetting property of a droplet standing on the graphite surface. Interestingly, the pancakes spontaneously displayed strong positively charged behavior. Theoretical studies showed that the formation of such positively charged pancakes is attributed to cation-? interactions between Na(+) ions in the aqueous solution and aromatic rings on the graphite surface, promoting the adsorption of water molecules together with cations onto the graphite surface; i.e., Na(+) ions as a medium adsorbed to the graphite surface through cation-? interactions on one side while at the same time bonding to water molecules through hydration interaction on the other side at a molecular scale. These findings suggest that actual interactions regarding carbon-based graphitic surfaces including those of graphene, carbon nanotubes, and biochar may be significantly different from existing theory and they provide new insight into the control of surface wettability, interactions and related physical, chemical and biological processes.
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Role of the MAPKs/TGF-?1/TRAF6 Signaling Pathway in Atrial Fibrosis of Patients with Chronic Atrial Fibrillation and Rheumatic Mitral Valve Disease.
Cardiology
PUBLISHED: 06-03-2014
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Objective: Atrial remodeling is involved in atrial fibrillation (AF), and atrial fibrosis is an important marker of atrial remodeling. On the basis of our previous animal studies of the mitogen-activated protein kinases (MAPKs)/transforming growth factor ?1 (TGF-?1)/tumor necrosis factor pathway in atrial fibrosis, we undertook investigation of this signaling pathway in atrial fibrosis of patients with chronic AF (CAF) and rheumatic mitral valve disease. Methods: Fifty-six rheumatic mitral valve disease patients were divided into CAF (course of AF >12 months) and sinus rhythm (SR) groups. Left atrial appendage tissue was collected during heart surgery, and pathological examination was done to evaluate atrial fibrosis. Protein and mRNA expression of TGF-?1, TRAF6 and connective tissue growth factor (CTGF) and protein expression of phosphorylated MAPKs and TGF-?-activated kinase 1 (TAK1) were measured. Results: Histological examination revealed that the severity of atrial fibrosis in CAF patients was significantly higher, mRNA and protein expression of TGF-?1, TRAF6 and CTGF in CAF were significantly increased, and the protein expression of phosphorylated MAPKs and TAK1 was significantly increased in CAF compared to SR patients. Conclusion: The MAPKs/TGF-?1/TRAF6 signaling pathway is involved in atrial fibrosis of CAF patients, and TRAF6 may become a new target for the treatment of atrial fibrosis. © 2014 S. Karger AG, Basel.
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Posterior iliac crescent fracture-dislocation: is it only rotationally unstable?
Orthopedics
PUBLISHED: 05-10-2014
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Posterior iliac crescent fracture-dislocation is generally considered rotationally unstable and vertically stable. The current study (1) investigated whether vertical instability may occur in posterior iliac crescent fracture-dislocation and (2) analyzed the clinical features of vertically unstable iliac crescent fracture-dislocation as well as treatment strategies. Patients with pelvic fracture who were treated in the authors' department from June 2009 to June 2012 were retrospectively reviewed. This study analyzed the clinical features, including incidence, hemodynamic state, associated injuries, injury severity score, and treatment methods for vertically unstable iliac crescent fracture-dislocation. Four patients had vertically unstable fracture-dislocation, accounting for 12.9% of all iliac crescent fracture-dislocations. All 4 patients were hemodynamically unstable on admission and had complications of associated injuries with a higher injury severity score. In 3 of the 4 patients, iliac crescent fracture-dislocations were reduced via the posterior approach at the initial stage and these patients underwent fixation with a plate. The remaining patient was initially given transcondylar traction because of severe complications and underwent open reduction and internal fixation (ORIF) via a posterior approach at a later stage. The outcomes of all 4 patients were rated as good or excellent by the Kobbe rating system at the last follow-up. Vertical instability may occur in iliac crescent fracture-dislocation. The authors propose ORIF of the fracture-dislocation via a posterior approach. When initial surgery is not possible because of severe associated organ injuries, the authors propose transcondylar traction to allow reduction of the sacroiliac joint and ORIF at a later stage.
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Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing.
Nat Commun
PUBLISHED: 05-01-2014
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Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome sequencing of 49 GCs with diffuse (N=31) and intestinal (N=18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.
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Cathepsin D Repairing Role in Photodamaged Skin Barrier.
Skin Pharmacol Physiol
PUBLISHED: 04-26-2014
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Backgrounds/Objectives: Cathepsin D plays an important part in maintaining a normal skin barrier. Our previous study found that cathepsin D decreased in chronic photodamaged skin. This study investigated the cathepsin D content change in the stratum corneum (SC) and the repairing role of cathepsin D in chronic photodamaged skin barrier via the application of cathepsin D gel. Methods: Cathepsin D gel (0.001%) was applied to chronic photodamaged (sun-exposed forearm) human skin on identical sites (1 cm²/area) twice daily for 2 weeks. At 30 min and at 1, 3, 7, and 14 days, skin hydration and transepidermal water loss (TEWL) average values were detected via noninvasive skin detection equipment. Cathepsin D and transglutaminase (TGase)-1 in the skin sublayers were separated and detected via tape stripping, ELISA and Western blot. Results: After 2 weeks of cathepsin D gel application, the skin moisture value increased from 86.8 ± 1.2 to 95.2 ± 2.7 (p < 0.05), while TEWL decreased from 17.88 ± 1.87 to 11.58 ± 2.14 (p < 0.05). Cathepsin D protein was detected in the upper epidermis (12.6 ± 2.6 ng/cm(2)), mid-epidermis (8.4 ± 0.8 ng/cm(2)) and deep epidermis (16.2 ± 2.6 ng/cm(2)) in the cathepsin D gel group compared to the control group (2.2 ± 0.7, 3.0 ± 1.1 and 3.85 ± 1.4 ng/cm(2), respectively; p < 0.05). TGase-1 enzyme expression was upregulated 2.54 ± 0.19 times in the matrix gel-treated skin. Conclusions: These data suggest that cathepsin D gel could increase the SC cathepsin D content and repair the epidermal barrier in chronic photodamaged skin. The mechanism might be related to increasing TGase-1 expression and activity. © 2014 S. Karger AG, Basel.
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Genomic analysis and expression investigation of caleosin gene family in Arabidopsis.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-16-2014
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Caleosin is a common lipid-droplet surface protein, which has the ability to bind calcium. Arabidopsis (Arabidopsis thaliana) is considered a model organism in plant researches. Although there are growing researches about caleosin in the past few years, a systemic analysis of caleosins in Arabidopsis is still scarce. In this study, a comprehensive investigation of caleosins in Arabidopsis was performed by bioinformatics methods. Firstly, eight caleosins in Arabidopsis are divided into two types, L-caleosin and H-caleosin, according to their molecular weights, and these two types of caleosin have many differences in characteristics. Secondly, phylogenetic tree result indicates that L-caleosin may evolve from H-caleosin. Thirdly, duplication pattern analysis shows that segmental and tandem duplication are main reasons for Arabidopsis caleosin expansion with the equal part. Fourthly, the expression profiles of caleosins are also investigated in silico in different organs and under various stresses and hormones. In addition, based on promoter analysis, caleosin may be involved in calcium signal transduction and lipid accumulation. Thus, the classification and expression analysis of caleosin genes in Arabidopsis provide facilities to the research of phylogeny and functions in this gene family.
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Micromonospora zeae sp. nov., a novel endophytic actinomycete isolated from corn root (Zea mays L.).
J. Antibiot.
PUBLISHED: 04-02-2014
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A novel actinomycete, designated strain NEAU-gq9(T), was isolated from corn root (Zea mays L.) and characterized using a polyphasic approach. The organism was found to have morphological and chemotaxonomic characteristics typical of the genus Micromonospora. On the basis of 16S rRNA gene sequence similarity studies, strain NEAU-gq9(T) was most closely related to Micromonospora zamorensis CR38(T) (99.3%), Micromonospora jinlongensis NEAU-GRX11(T) (99.2%), Micromonospora saelicesensis Lupac 09(T) (99.2%), Micromonospora chokoriensis 2-19(6)(T) (98.9%), Micromonospora coxensis 2-30-b(28)(T) (98.6%) and Micromonospora lupini Lupac 14N(T) (98.5%). Phylogenetic analysis based on the 16S rRNA gene and gyrB gene demonstrated that strain NEAU-gq9(T) is a member of the genus Micromonospora and supported the closest phylogenetic relationship to M. zamorensis CR38(T), M. jinlongensis NEAU-GRX11(T), M. saelicesensis Lupac 09(T), M. chokoriensis 2-19(6)(T) and M. lupini Lupac 14N(T). A combination of DNA-DNA hybridization, morphological and physiological characteristics indicated that the novel strain could be readily distinguished from the closest phylogenetic relatives. Therefore, it is proposed that strain NEAU-gq9(T) represents a novel species of the genus Micromonospora, for which the name Micromonospora zeae sp. nov. is proposed. The type strain is NEAU-gq9(T) (=CGMCC 4.7092(T)=DSM 45882(T)).The Journal of Antibiotics advance online publication, 21 May 2014; doi:10.1038/ja.2014.54.
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The diversity of quasars unified by accretion and orientation.
Nature
PUBLISHED: 03-30-2014
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Quasars are rapidly accreting supermassive black holes at the centres of massive galaxies. They display a broad range of properties across all wavelengths, reflecting the diversity in the physical conditions of the regions close to the central engine. These properties, however, are not random, but form well-defined trends. The dominant trend is known as 'Eigenvector 1', in which many properties correlate with the strength of optical iron and [O III] emission. The main physical driver of Eigenvector 1 has long been suspected to be the quasar luminosity normalized by the mass of the hole (the 'Eddington ratio'), which is an important parameter of the black hole accretion process. But a definitive proof has been missing. Here we report an analysis of archival data that reveals that the Eddington ratio indeed drives Eigenvector 1. We also find that orientation plays a significant role in determining the observed kinematics of the gas in the broad-line region, implying a flattened, disk-like geometry for the fast-moving clouds close to the black hole. Our results show that most of the diversity of quasar phenomenology can be unified using two simple quantities: Eddington ratio and orientation.
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The effect of postural correction and subsequent balloon inflation in deformity correction of acute osteoporotic vertebral fractures.
J Korean Neurosurg Soc
PUBLISHED: 03-29-2014
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To determine deformity correction by postural correction and subsequent balloon inflation in acute vertebral compression fractures (OVCFs) and to examine the effect of bone mineral density on deformity correction.
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The pathogen Candida albicans hijacks pyroptosis for escape from macrophages.
MBio
PUBLISHED: 03-27-2014
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The fungal pathogen Candida albicans causes macrophage death and escapes, but the molecular mechanisms remained unknown. Here we used live-cell imaging to monitor the interaction of C. albicans with macrophages and show that C. albicans kills macrophages in two temporally and mechanistically distinct phases. Early upon phagocytosis, C. albicans triggers pyroptosis, a proinflammatory macrophage death. Pyroptosis is controlled by the developmental yeast-to-hypha transition of Candida. When pyroptosis is inactivated, wild-type C. albicans hyphae cause significantly less macrophage killing for up to 8 h postphagocytosis. After the first 8 h, a second macrophage-killing phase is initiated. This second phase depends on robust hyphal formation but is mechanistically distinct from pyroptosis. The transcriptional regulator Mediator is necessary for morphogenesis of C. albicans in macrophages and the establishment of the wild-type surface architecture of hyphae that together mediate activation of macrophage cell death. Our data suggest that the defects of the Mediator mutants in causing macrophage death are caused, at least in part, by reduced activation of pyroptosis. A Mediator mutant that forms hyphae of apparently wild-type morphology but is defective in triggering early macrophage death shows a breakdown of cell surface architecture and reduced exposed 1,3 ?-glucan in hyphae. Our report shows how Candida uses host and pathogen pathways for macrophage killing. The current model of mechanical piercing of macrophages by C. albicans hyphae should be revised to include activation of pyroptosis by hyphae as an important mechanism mediating macrophage cell death upon C. albicans infection. IMPORTANCE Upon phagocytosis by macrophages, Candida albicans can transition to the hyphal form, which causes macrophage death and enables fungal escape. The current model is that the highly polarized growth of hyphae results in macrophage piercing. This model is challenged by recent reports of C. albicans mutants that form hyphae of wild-type morphology but are defective in killing macrophages. We show that C. albicans causes macrophage cell death by at least two mechanisms. Phase 1 killing (first 6 to 8 h) depends on the activation of the pyroptotic programmed host cell death by fungal hyphae. Phase 2 (up to 24 h) is rapid and depends on robust hyphal formation but is independent of pyroptosis. Our data provide a new model for how the interplay between fungal morphogenesis and activation of a host cell death pathway mediates macrophage killing by C. albicans hyphae.
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Maintaining glycogen synthase kinase-3 activity is critical for mTOR kinase inhibitors to inhibit cancer cell growth.
Cancer Res.
PUBLISHED: 03-13-2014
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mTOR kinase inhibitors that target both mTORC1 and mTORC2 are being evaluated in cancer clinical trials. Here, we report that glycogen synthase kinase-3 (GSK3) is a critical determinant for the therapeutic response to this class of experimental drugs. Pharmacologic inhibition of GSK3 antagonized their suppressive effects on the growth of cancer cells similarly to genetic attenuation of GSK3. Conversely, expression of a constitutively activated form of GSK3? sensitized cancer cells to mTOR inhibition. Consistent with these findings, higher basal levels of GSK3 activity in a panel of human lung cancer cell lines correlated with more efficacious responses. Mechanistic investigations showed that mTOR kinase inhibitors reduced cyclin D1 levels in a GSK3?-dependent manner, independent of their effects on suppressing mTORC1 signaling and cap binding. Notably, selective inhibition of mTORC2 triggered proteasome-mediated cyclin D1 degradation, suggesting that mTORC2 blockade is responsible for GSK3-dependent reduction of cyclin D1. Silencing expression of the ubiquitin E3 ligase FBX4 rescued this reduction, implicating FBX4 in mediating this effect of mTOR inhibition. Together, our findings define a novel mechanism by which mTORC2 promotes cell growth, with potential implications for understanding the clinical action of mTOR kinase inhibitors.
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Rapid screening for sickle cell disease by polymerase chain reaction-high resolution melting analysis.
Mol Med Rep
PUBLISHED: 03-05-2014
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Each year, ~300,000 individuals with sickle cell disease (SCD), a hemoglobinopathy caused by ?-globin gene mutation, are born, and >75% of those are in Africa. The present study examined 511 individuals on the island of Bioko (Equatorial Guinea) and attempted to establish a method for rapid sickle cell disease screening. Following DNA extraction and polymerase chain reaction (PCR) amplification, high resolution melting (HRM) analysis was used to assess the specificity of fluorescence signals of the PCR products and to differentiate various genotypes of these products. The analytical results of HRM were validated using DNA sequencing. By HRM analysis, 80 out of 511 samples were classified as hemoglobin S (Hb S) heterozygotes, while 431 out of 511 samples were classified as wild-type. No mutant homozygote was identified. DNA sequencing indicated that within the 431 wild-type samples as indicated by HRM analysis, one case was actually a Hb S heterozygote and another case was a rare hemoglobin S-C genotype (sickle-hemoglobin C disease). One out of 80 suspected Hb S heterozygotes as indicated by HRM was confirmed as wild-type by DNA sequencing and the results of residual 508 cases were consistent for HRM analysis and sequencing. In conclusion, HRM analysis is a simple, high-efficiency approach for Hb S screening and is useful for early diagnosis of SCD and particularly suitable for application in the African area.
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Actinomycetospora atypica sp. nov., a novel soil actinomycete and emended description of the genus Actinomycetospora.
Antonie Van Leeuwenhoek
PUBLISHED: 02-19-2014
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A novel actinomycete, designated strain NEAU-st4(T), was isolated from a soil sample collected from Shaanxi province, Northwest China and characterized using a polyphasic approach. 16S rRNA gene sequence analysis revealed that strain NEAU-st4(T) has the highest sequence similarities with Actinomycetospora rishiriensis RI109-Li102(T) (99.4 %), Actinomycetospora corticicola 014-5(T) (99.1 %), Actinomycetospora chiangmaiensis YIM 0006(T) (98.8 %) and Actinomycetospora iriomotensis IR73-Li102(T) (98.2 %). However, the low level of DNA-DNA relatedness differentiated strain NEAU-st4(T) from its closest phylogenetic neighbours. The main chemotaxonomic properties of strain NEAU-st4(T), such as the diamino acid of the peptidoglycan, the whole-cell hydrolysates, the predominant menaquinones and the phospholipid profile, supported its classification within the genus Actinomycetospora. The distinctive morphology of this strain compared with that of other members in the genus Actinomycetospora is the formation of sporangia directly on the substrate hyphae. Phenotypic and genotypic differences also allowed the distinction of the strain from closely related species. Consequently, strain NEAU-st4(T) represents a new species of the genus Actinomycetospora, for which the name Actinomycetospora atypica sp. nov. is proposed. The type strain is NEAU-st4(T) (=CGMCC 4.7093(T) = DSM 45873(T)).
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An obesity genetic risk score predicts risk of insulin resistance among Chinese children.
Endocrine
PUBLISHED: 02-14-2014
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A great number of body mass index (BMI)/obesity-related loci have been identified by recent genome-wide association studies. The objective of the study is to investigate the associations of 11 obesity-related loci with insulin resistance (IR) in a Chinese children population. Participants included 3,468 Chinese children, aged 6-18 years. The 75 percentile (equal to 2.93) of homeostasis model assessment of IR (HOMA-IR) index was considered as the cut-off of IR. A total of 868 IR cases and 2,600 control children were identified. In age- and sex-adjusted model, only two SNPs in/near GNPDA2 and KCTD15 genes were significantly associated with risk of IR [GNPDA2 rs10938397: allelic odds ratio (OR) = 1.19, 95 % confidence interval (CI) 1.06-1.34, P = 0.003; KCTD15 rs29941: allelic OR = 1.15, 95 % CI = 1.01-1.31, P = 0.034]; genetic risk score was also significantly associated risk of IR (OR = 1.08, 95 % 1.04-1.12, P = 1.18 × 10(-4)). After additional adjustment for BMI, none remained significant. The associations of GNPDA2 rs10938397 and the SNPs in combination with risk of IR remained statistically significant after correction for multiple testing. The present study demonstrated that the associations of GNPDA2 rs10938397 and the SNPs in combination with risk of IR were statistically significant, which were dependent on BMI.
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A global virulence regulator in Acinetobacter baumannii and its control of the phenylacetic acid catabolic pathway.
J. Infect. Dis.
PUBLISHED: 01-14-2014
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Acinetobacter baumannii is one of the most notorious hospital-acquired pathogens, and novel treatment strategies are desperately required. Two-component regulatory systems represent potential therapeutic targets as they mediate microorganism adaptation to changing environments, often control virulence, and are specific to bacteria. Here we describe the first global virulence regulator in A. baumannii.
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Bioactive calcium sulfate/magnesium phosphate cement for bone substitute applications.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 01-14-2014
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A novel calcium sulfate/magnesium phosphate cement (CSMPC) composite was prepared and studied in the present work. The physical properties including the phases, the microstructures, the setting properties and the compressive strengths of the CSMPCs were studied. The bio-performances of the CSMPCs were comprehensively evaluated using in vitro simulated body fluid (SBF) method and in vitro cell culture. The dependence of the physical and chemical properties of the CSMPC on its composition and microstructure was studied in detail. It is found that the CSMPC composites exhibited mediate setting times (6-12 min) compared to the calcium sulfate (CS) and the magnesium phosphate cement (MPC). They showed an encapsulation structure in which the unconverted hexagonal prism CSH particles were embedded in the xerogel-like MPC matrix. The phase compositions and the mechanical properties of the CSMPCs were closely related to the content of MPC and the hardening process. The CSMPCs exhibited excellent bioactivity and good biocompatibility to support the cells to attach and proliferate on the surface. The CSMPC composite has the potential to serve as bone grafts for the bone regeneration.
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Efficient construction of unmarked recombinant mycobacteria using an improved system.
J. Microbiol. Methods
PUBLISHED: 01-09-2014
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The genetic study of mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium ulcerans, is hampered heavily by their slow growth. We have developed efficient, versatile, and improved genetic tools for constructing unmarked recombinant mycobacteria more rapidly including generating multiple mutants using the same antibiotic marker in both fast- and slow-growing mycobacteria.
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Plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice.
J Transl Med
PUBLISHED: 01-07-2014
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Most tympanic membrane (TM) perforations heal spontaneously, but approximately 10-20% remain open as chronic TM perforations. Chronic perforations can lead to an impaired hearing ability and recurrent middle ear infections. Traditionally, these perforations must be surgically closed, which is costly and time consuming. Therefore, there is a need for simpler therapeutic strategies. Previous studies by us have shown that plasminogen (plg) is a potent pro-inflammatory regulator that accelerates cutaneous wound healing in mice. We have also shown that the healing of TM perforations is completely arrested in plg-deficient (plg(-/-)) mice and that these mice develop chronic TM perforations. In the present study, we investigated the therapeutic potential of local plg injection in acute and chronic TM perforation mice models.
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Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.
PLoS ONE
PUBLISHED: 01-01-2014
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Cathepsin K (CatK), a cysteine protease with the potent elastolytic activity, plays a predominant role in intracellular elastin degradation in human dermal fibroblasts (HDFs), and contributes to solar elastosis. In previous studies, CatK expression was downregulated in photoaged skin and fibroblasts, but upregulated in acute UVA-irradiated skin and fibroblasts. The underlying mechanisms regulating UVA-induced CatK expression remain elusive.
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Age- and sex-dependent association between FTO rs9939609 and obesity-related traits in Chinese children and adolescents.
PLoS ONE
PUBLISHED: 01-01-2014
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The associations between common variants in the fat mass- and obesity-associated (FTO) gene and obesity-related traits may be age-dependent and may differ by sex. The present study aimed to assess the association of FTO rs9939609 with body mass index (BMI) and the risk of obesity from childhood to adolescence, and to determine the age at which the association becomes evident.
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Krüppel-like transcription factor 11 (KLF11) overexpression inhibits cardiac hypertrophy and fibrosis in mice.
Biochem. Biophys. Res. Commun.
PUBLISHED: 11-26-2013
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The Krüppel-like factors (KLFs) belong to a subclass of Cys2/His2 zinc-finger DNA-binding proteins. The KLF family member KLF11 is originally identified as a transforming growth factor ? (TGF-?)-inducible gene and is one of the most studied in this family. KLF11 is expressed ubiquitously and participates in diabetes and regulates hepatic lipid metabolism. However, the role of KLF11 in cardiovascular system is largely unknown. Here in this study, we reported that KLF11 expression is down-regulated in failing human hearts and hypertrophic murine hearts. To evaluate the roles of KLF11 in cardiac hypertrophy, we generated cardiac-specific KLF11 transgenic mice. KLF11 transgenic mice do not show any difference from their littermates at baseline. However, cardiac-specific KLF11 overexpression protects mice from TAC-induced cardiac hypertrophy, with reduced radios of heart weight (HW)/body weight (BW), lung weight/BW and HW/tibia length, decreased left ventricular wall thickness and increased fractional shortening. We also observe lower expression of hypertrophic fetal genes in TAC-challenged KLF11 transgenic mice compared with WT mice. In addition, KLF11 reduces cardiac fibrosis in mice underwent hypertrophy. The expression of fibrosis markers are also down-regulated when KLF11 is overexpressed in TAC-challenged mice. Taken together, our findings identify a novel anti-hypertrophic and anti-fibrotic role of KLF11, and KLF11 activator may serve as candidate drug for heart failure patients.
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Differential expression and regulation of Tdo2 during mouse decidualization.
J. Endocrinol.
PUBLISHED: 11-06-2013
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Tryptophan 2,3-dioxygenase (Tdo2) is a rate-limiting enzyme which directs the conversion of tryptophan to kynurenine. The aim of this study was to examine the expression and regulation of Tdo2 in mouse uterus during decidualization. Tdo2 mRNA was mainly expressed in the decidua on days 6-8 of pregnancy. By real-time PCR, a high level of Tdo2 expression was observed in the uteri from days 6 to 8 of pregnancy, although Tdo2 expression was observed on days 1-8. Simultaneously, Tdo2 mRNA was also detected under in vivo and in vitro artificial decidualization. Estrogen, progesterone, and 8-bromoadenosine-cAMP could induce the expression of Tdo2 in the ovariectomized mouse uterus and uterine stromal cells. Tdo2 could regulate cell proliferation and stimulate the expression of decidual marker Dtprp in the uterine stromal cells and decidual cells. Overexpression of Tdo2 could upregulate the expression of Ahr, Cox2, and Vegf genes in uterine stromal cells, while Tdo2 inhibitor 680C91 could downregulate the expression of Cox2 and Vegf genes in uterine decidual cells. These data indicate that Tdo2 may play an important role during mouse decidualization and be regulated by estrogen, progesterone, and cAMP.
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Guanylated polymethacrylates: a class of potent antimicrobial polymers with low hemolytic activity.
Biomacromolecules
PUBLISHED: 10-25-2013
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We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide mimics). To investigate the structure-activity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition-fragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity.
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[Risk of obesity-related gene polymorphism on the incidence and durative of childhood obesity].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 10-16-2013
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To examine the impact of single nucleotide polymorphisms(SNPs)in obesity-related genes on the incidence and durative of obesity in childhood and adolescence.
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A photo-driven polyoxometalate complex shuttle and its homogeneous catalysis and heterogeneous separation.
J. Am. Chem. Soc.
PUBLISHED: 09-23-2013
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A "smart" core-shell complex is designed to combine a catalytic reaction and automatic separation through remote light control. Here, we present the induced amphiphilic behavior of a surfactant-encapsulated polyoxometalate complex with photoresponsive azobenzene units on the periphery. The reversible phase transfer of the complex shuttle between two incompatible phase termini, driven by a photoisomerization-induced polarity change, further facilitates the separation and recycle of the catalyst.
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FTIR spectroscopic studies of lithium tetrafluoroborate in propylene carbonate+diethyl carbonate mixtures.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 09-17-2013
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FTIR (Fourier transformed infrared) spectra have been collected and analyzed for solutions of lithium tetrafluoroborate in propylene carbonate (PC), diethyl carbonate (DEC), and PC+DEC mixtures. It has been shown that the carbonyl stretch bands of PC and DEC, the ring of PC and the ether oxygen stretch bands of DEC are all very sensitive to the interaction between Li(+) and the solvent molecules. New shoulders appear and the original bands split with the addition of LiBF4, indicating that a strong interaction between Li(+) and molecules of PC and DEC exists through the oxygen group of CO and ring of PC and both CO oxygen and ether oxygen atoms of DEC. In addition, no preferential solvation of Li(+) in LiBF4/PC+DEC solutions was detected.
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Chiral self-assembly and reversible light modulation of a polyoxometalate complex via host-guest recognition.
Chem. Commun. (Camb.)
PUBLISHED: 09-12-2013
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Chiral self-assembly of an azobenzene-grafted POM complex has been constructed through self-crosslinking by both the electrostatic and host-guest interactions and reversibly modulated by dynamic controlling of the isomerization of photoactive groups in the complex.
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[Characteristics of evapotranspiration and crop coefficient of agroecosystems in semi-arid area of Loess Plateau, Northwest China].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 09-11-2013
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Evapotranspiration (ET) is an important component of ground surface energy balance and water balance, and closely related to water cycle. By using eddy covariance technique, this paper studied the ET characteristics of agroecosystems in the semi-arid area of Loess Plateau in growth season (from April to September), 2010, and analyzed the relationships between crop coefficient and environmental factors. During the observation period, the diurnal variation of latent heat flux (LE) in each month was similar to single-peak curve, and the peak value (151.4 W x m(-2)) occurred in August. The daytime energy partitioning manner showed a significant seasonal variation, with LE/R(n) < H/R(n) (R(n) was net radiation, and H was sensible heat flux) from April to June, and LE/R(n) > H/R(n) from July to September. The daily ET rate also showed a significant seasonal variation, with the maximum of 4.69 mm x d(-1). The wind speed (W(s)), relative humidity (RH), soil water content (theta), and atmospheric vapor pressure deficit (D) were the major factors affecting the crop coefficient K(c) which was exponentially decreased with increasing W(s), exponentially increased with increasing RH and theta, and linearly decreased with increasing D.
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The E3 ubiquitin ligases ?-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis.
Mol. Cancer
PUBLISHED: 08-29-2013
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The novel Akt inhibitor, API-1, induces apoptosis through undefined mechanisms. The current study focuses on revealing the mechanisms by which API-1 induces apoptosis.
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Cordycepin prevented IL-?-induced expression of inflammatory mediators in human osteoarthritis chondrocytes.
Int Orthop
PUBLISHED: 08-15-2013
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Cordycepin, a nucleoside derivative isolated from Cordyceps, has been reported to exert anti-inflammatory, antitumor, antidiabetic and renoprotective effects. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. This study aimed to assess the effects of cordycepin on human OA chondrocytes.
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Increased osteopontin expression is associated with progression from vulvar precancerous lesions to vulvar squamous cell carcinoma.
Arch. Gynecol. Obstet.
PUBLISHED: 08-07-2013
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Vulvar squamous cell carcinoma (VSCC) contributes to about 3-5 % of all gynecological cancers. Vulvar intraepithelial neoplasia (VIN) and vulvar lichen sclerosus (VLS) are regarded as precancerous lesions. Early detection and treatment of precancerous lesions may prevent development of VSCC. Osteopontin (OPN) has been shown to be involved in many physiological and pathological processes, such as tumor progression, by promoting cancer cell invasion and metastasis. As a result of these findings, OPN has been described as a potential marker for tumor progression in some malignancies. In this study, we investigated the expression of OPN in vulvar tissue specimens and compared its expression between different histopathological grades.
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Key role for the transcriptional factor, osterix, in spine development.
Spine J
PUBLISHED: 08-06-2013
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Osterix (Osx) is an important transcriptional factor for bone formation; however, its role in spine development has not been determined.
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Asymmetric Facet Joint Osteoarthritis and its Relationships to Facet Orientation, Facet Tropism and Ligamentum Flavum Thickening.
J Spinal Disord Tech
PUBLISHED: 08-02-2013
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The degrees of osteoarthritis of the left and right facet joints were evaluated by using computerized tomography (CT) among elderly patients with low back or leg pain.
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Emerging rules for effective antimicrobial coatings.
Trends Biotechnol.
PUBLISHED: 07-31-2013
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In order to colonize abiotic surfaces, bacteria and fungi undergo a profound change in their biology to form biofilms: communities of microbes embedded into a matrix of secreted macromolecules. Despite strict hygiene standards, biofilm-related infections associated with implantable devices remain a common complication in the clinic. Here, the application of highly dosed antibiotics is problematic in that the biofilm (i) provides a protective environment for microbes to evade antibiotics and/or (ii) can provide selective pressure for the evolution of antibiotic-resistant microbes. However, recent research suggests that effective prevention of biofilm formation may be achieved by multifunctional surface coatings that provide both non-adhesive and antimicrobial properties imparted by antimicrobial peptides. Such coatings are the subject of this review.
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An obesity genetic risk score is associated with metabolic syndrome in Chinese children.
Gene
PUBLISHED: 07-27-2013
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Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with body mass index (BMI)/obesity. In this study, we aim to examine the associations of obesity related loci with risk of metabolic syndrome (MetS) in a children population from China. A total of 431 children with MetS and 3046 controls were identified based on the modified ATPIII definition. 11 SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, BDNF rs6265, FAIM2 rs7138803, NPC1 rs1805081, SEC16B rs10913469, SH2B1 rs4788102, PCSK1rs6235, KCTD15 rs29941, BAT2 rs2844479) were genotyped by TaqMan 7900. Of 11 SNPs, GNPDA2 rs10938397, BDNF rs6265, and FAIM2 rs7138803 were nominally associated with risk of MetS (GNPDA2 rs10938397: odds ratio (OR)=1.21, 95% confidence interval (CI)=1.04-1.40, P=0.016; BDNF rs6265: OR=1.19, 95% CI=1.03-1.39, P=0.021; FAIM2 rs7138803: OR=1.20, 95% CI=1.02-1.40, P=0.025); genetic risk score (GRS) was significantly associated with risk of MetS (OR=1.09, 95% CI=1.04-1.15, P=5.26×10(-4)). After further adjustment for BMI, none of SNPs were associated with risk of MetS (all P>0.05); the association between GRS and risk of MetS remained nominally (OR=1.02, 95%CI=0.96-1.08, P=0.557). However, after correction for multiple testing, only GRS was statistically associated with risk of MetS in the model without adjustment for BMI. The present study demonstrated that there were nominal associations of GNPDA2 rs10938397, BDNF rs6265, and FAIM2 rs7138803 with risk of MetS. The SNPs in combination have a significant effect on risk of MetS among Chinese children. These associations above were mediated by adiposity.
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Nonomuraea shaanxiensis sp. nov., a novel actinomycete isolated from a soil sample.
Antonie Van Leeuwenhoek
PUBLISHED: 07-25-2013
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A novel actinomycete, strain NEAU-st1(T), was isolated from a soil sample collected in Shaanxi province, Northwest China and characterized using a polyphasic approach. 16S rRNA gene sequence similarity studies showed that strain NEAU-st1(T) belongs to the genus Nonomuraea, being most closely related to Nonomuraea rosea GW12687(T) (98.91 %), Nonomuraea solani NEAU-Z6(T) (98.44 %), Nonomuraea rhizophila YIM67092(T)(98.24 %) and Nonomuraea monospora PT708(T) (98.02 %); similarities to sequences of other type strains of the genus Nonomuraea were lower than 98 %. Both tree-making algorithms used also supported the position that strain NEAU-st1(T) formed a distinct clade with its most closely related species. Morphological and physiological characteristics confirmed that the strain belongs to the genus Nonomuraea and distinguished it from its most closely related species. DNA-DNA hybridization further differentiated strain NEAU-st1(T) from its nearest phylogenetic neighbours. These results suggested that strain NEAU-st1(T) represents a novel species of the genus Nonomuraea, for which the name Nonomuraea shaanxiensis sp. nov. is proposed. The type strain is NEAU-st1(T) (=CGMCC 4.7096(T) = DSM 45877(T)).
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Discovery of Dap-3 polymyxin analogues for the treatment of multidrug-resistant Gram-negative nosocomial infections.
J. Med. Chem.
PUBLISHED: 06-18-2013
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We report novel polymyxin analogues with improved antibacterial in vitro potency against polymyxin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa . In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.
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Common genetic variants associated with lipid profiles in a Chinese pediatric population.
Hum. Genet.
PUBLISHED: 06-15-2013
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Genome-wide association (GWA) studies have identified many candidate genes that are associated with blood lipid and lipoprotein concentrations. In this study, we want to know whether the results from European for lipid-related single-nucleotide polymorphisms (SNPs) are generalizable to Chinese children. We genotyped seven SNPs in Chinese school-age children (n = 3,503) and assessed the associations of these SNPs with lipids profiles and dyslipidemia. After false discovery rate correction, of the seven SNPs, six (rs2144300, p ~ 9.30 × 10(-3); rs1260333, p ~ 6.20 × 10(-11); rs1260326, p ~ 8.73 × 10(-11); rs10105606, p ~ 0.010; rs1748195, p ~ 0.016 and rs964184, p ~ 2.33 × 10(-13)) showed strong association with triglycerides. Three SNPs (rs1260333, p ~ 3.30 × 10(-3); rs1260326, p ~ 4.39 × 10(-3) and rs2954029, p ~ 6.36 × 10(-4)) showed strong association with total cholesterol. Two SNPs (rs10105606, p ~ 6.66 × 10(-4) and rs1748195, p ~ 2.55 × 10(-3)) showed strong association with high density lipoprotein cholesterol. Four SNPs (rs1260333, p ~ 0.017; rs1260326, p ~ 0.013; rs2954029, p ~ 1.09 × 10(-3) and rs964184, p ~ 5.51 × 10(-3)) showed strong association with low density lipoprotein cholesterol. There were significant associations between rs1260333 (OR is 0.82, 95 % CI 0.74-0.92, p ~ 3.96 × 10(-4)), rs1260326 (OR is 0.82, 95 % CI 0.74-0.92, p ~ 5.31 × 10(-4)), and rs964184 (OR is 1.36, 95 % CI 1.20-1.55, p ~ 1.89 × 10(-6)) and dyslipidemia. These SNPs generated strong combined effects on lipid profiles and dyslipidemia. Our study demonstrates that SNPs associated with lipids from European GWA studies also play roles in Chinese children, which broadened the understanding of lipids metabolism.
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Effects of extracellular calcium on viability and osteogenic differentiation of bone marrow stromal cells in vitro.
Hum. Cell
PUBLISHED: 06-08-2013
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Bone marrow stromal cells (BMSCs) have been extensively used for tissue engineering. However, the effect of Ca(2+) on the viability and osteogenic differentiation of BMSCs has yet to be evaluated. To determine the dose-dependent effect of Ca(2+) on viability and osteogenesis of BMSCs in vitro, BMSCs were cultured in calcium-free DMEM medium supplemented with various concentrations of Ca(2+) (0, 1, 2, 3, 4, and 5 mM) from calcium citrate. Cell viability was analyzed by MTT assay and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) assay, Von Kossa staining, and real-time PCR. Ca(2+) stimulated BMSCs viability in a dose-dependent manner. At slightly higher concentrations (4 and 5 mM) in the culture, Ca(2+) significantly inhibited the activity of ALP on days 7 and 14 (P < 0.01 or P < 0.05), significantly suppressed collagen synthesis (P < 0.01 or P < 0.05), and significantly elevated calcium deposition (P < 0.01) and mRNA levels of osteocalcin (P < 0.01 or P < 0.05) and osteopontin (P < 0.01 or P < 0.05). Therefore, elevated concentrations of extracellular calcium may promote cell viability and late-stage osteogenic differentiation, but may suppress early-stage osteogenic differentiation in BMSCs.
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Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance.
J. Cell. Sci.
PUBLISHED: 05-31-2013
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The extension of long slender axons is a key process of neuronal circuit formation, both during brain development and regeneration. For this, growth cones at the tips of axons are guided towards their correct target cells by signals. Growth cone behaviour downstream of these signals is implemented by their actin and microtubule cytoskeleton. In the first part of this Commentary, we discuss the fundamental roles of the cytoskeleton during axon growth. We present the various classes of actin- and microtubule-binding proteins that regulate the cytoskeleton, and highlight the important gaps in our understanding of how these proteins functionally integrate into the complex machinery that implements growth cone behaviour. Deciphering such machinery requires multidisciplinary approaches, including genetics and the use of simple model organisms. In the second part of this Commentary, we discuss how the application of combinatorial genetics in the versatile genetic model organism Drosophila melanogaster has started to contribute to the understanding of actin and microtubule regulation during axon growth. Using the example of dystonin-linked neuron degeneration, we explain how knowledge acquired by studying axonal growth in flies can also deliver new understanding in other aspects of neuron biology, such as axon maintenance in higher animals and humans.
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Establishing a target exposure for once-daily intravenous busulfan given with fludarabine and thymoglobulin before allogeneic transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-27-2013
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A combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated and effective in patients undergoing allogeneic hematopoietic stem cell transplantation. Although there is some evidence that Bu exposures exceeding 6000 ?M/min may lead to excessive toxicity, there is little information on the effect of exposures below this level on outcomes. We studied Bu exposure, as measured by area under the concentration-time curve (AUC), in 158 patients with various hematologic malignancies in an attempt to identify an optimal range for targeted therapy. The preparative chemotherapy regimen comprised Flu 50 mg/m(2) on days -6 to -2 and i.v. Bu 3.2 mg/kg on days -5 to -2 inclusive. Graft-versus-host disease (GVHD) prophylaxis included methotrexate, cyclosporin A, and antithymocyte globulin. Patients with Bu exposures below the median AUC of 4439 ?M/min were at increased risk for acute GVHD grade II-IV (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.19 to 4.49; P = .014). Those in the highest and lowest Bu exposure quartiles (daily AUC <3814 ?M/min and >4993 ?M/min) had an increased risk of nonrelapse mortality (subdistribution HR, 3.32; 95% CI, 1.46 to 7.54; P = .004), as well as worse disease-free survival (HR, 1.81; 95% CI, 1.09 to 2.99; P = .021) and overall survival (HR, 1.94; 95% CI, 1.12 to 3.37; P = .018). Bu exposures between 4440 and 4993 ?M/min were accompanied by the lowest risk of both nonrelapse mortality and acute GVHD.
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Intermolecular Visible-Light Photoredox Atom-Transfer Radical [3+2]-Cyclization of 2-(Iodomethyl)cyclopropane-1,1-dicarboxylate with Alkenes and Alkynes.
Chemistry
PUBLISHED: 05-20-2013
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Radical chemistry! A visible-light-promoted, tin/boron-free intermolecular [3+2] atom-transfer radical cyclization reaction was developed by using iridium polyphenylpridinyl complex as the sensitizer. 2-(Iodomethyl)cyclopropane-1,1-dicarboxylate reacted with various alkenes and alkynes to form cyclopentane and cyclopentene derivatives.
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Effects of PTHrP on expression of MMP9 and MMP13 in sika deer antler chondrocytes.
Cell Biol. Int.
PUBLISHED: 05-13-2013
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Deer antlers are the only mammalian appendages to display an annual cycle of full regeneration. However, little is known about the molecular mechanisms of antler regeneration. Our previous study has demonstrated that parathyroid hormone-related peptide (PTHrP) can promote proliferation of antler chondrocytes and inhibit its differentiation, but the mechanism underlying such regulation is not fully understood. We have determined the role of PTHrP on the mRNA expression of matrix metalloproteinase-9 (MMP9) and MMP13 in the antler chondrocytes. The possible pathways that transduce PTHrP effects were examined. In situ hybridization showed that MMP9 and MMP13 were mainly localized in the dermal fibroblasts, perichondrium, and cartilage in the sika deer antler, of which MMP9 and MMP13 were highly expressed in the chondrocytes. Exogenous PTHrP could inhibit the expression of MMP9 and MMP13 in the antler chondrocytes. The inhibitory effect of PTHrP on MMP9 was abolished by JNK inhibitor, SP600125, while P38MAPK inhibitor SB203850 and PKC inhibitor GF109203X could rescue the inhibitory effect of PTHrP on MMP13. The results suggest that PTHrP can inhibit MMP9 expression by JNK signaling pathway and MMP13 expression by p38MAPK and PKC signaling pathways in the antler chondrocytes. Thus PTHrP is involved in the control of antler chondrocytes maturation and cartilage matrix degradation.
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cis-2,3-Disubstituted cyclopropane 1,1-diesters in [3 + 2] annulations with aldehydes: highly diastereoselective construction of densely substituted tetrahydrofurans.
J. Org. Chem.
PUBLISHED: 05-09-2013
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A series of cis-2,3-disubstituted cyclopropane 1,1-diesters were examined in the AlCl3-promoted [3 + 2]-annulations with aldehydes. In this reaction, these cis-cyclopropanes displayed reactivities starkly different from their trans counterparts in terms of the high chemical yields (up to 98%) and provided the desired annulation products with excellent diastereomeric purity. This protocol provides a facile and highly stereoselective way to construct synthetically useful pentasubstituted tetrahydrofurans not easily accessible using other methods.
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The influence of anhedonia on feedback negativity in major depressive disorder.
Neuropsychologia
PUBLISHED: 05-02-2013
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Anhedonia is associated with reward-processing deficits of the dopamine system, which may increase the risk of depression. Nevertheless, few previous studies have examined the influence of hedonic tone on event-related potential (ERP) measures of reward processing in major depressive disorder. A simple gambling task was used to elicit feedback negativity (FN), an ERP component elicited by feedback indicating gain versus loss, in 27 patients with major depression and 27 healthy participants. We found that participants with depression were characterized by reduced FN responses, especially towards monetary gains, but not losses, compared with healthy individuals. In addition, the amplitude of FN to gain feedback in participants with depression was related to anhedonia severity and depressive symptoms. These findings indicate an association between low hedonic capacity and reduction in FN. As a neural measure of reward sensitivity, FN may be generated in part by reward-related activity.
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Influence of obesity on association between genetic variants identified by genome-wide association studies and hypertension risk in Chinese children.
Am. J. Hypertens.
PUBLISHED: 04-16-2013
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Childhood hypertension is a complex disease influenced by both genetic and environmental factors. We aimed to examine how obesity status influences the association of 6 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWASs) with systolic/diastolic blood pressure (SBP/DBP) and hypertension in Chinese children.
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Sex-dependent associations of genetic variants identified by GWAS with indices of adiposity and obesity risk in a Chinese children population.
Clin. Endocrinol. (Oxf)
PUBLISHED: 04-13-2013
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Recent genome-wide association studies have identified a few single nucleotide polymorphisms (SNPs), which are associated with body mass index (BMI)/obesity. This study aimed to examine the identified associations among a population of Chinese children.
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