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Find video protocols related to scientific articles indexed in Pubmed.
Lanreotide-conjugated PEG-DSPE micelles: an efficient nanocarrier targeting to somatostatin receptor positive tumors.
J Drug Target
PUBLISHED: 11-05-2014
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Abstract Lanreotide is an octapeptide analog of endogenous somatostatin, specifically binding with tumors over-express somatostatin receptor 2 (SSTR2). In this study, we conjugated lanreotide to 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (poly-(ethylene glycol))-2000] (PEG-DSPE), constructed active targeted micelles (lanreotide-PM), characterized their in vitro and in vivo targeting effect, and explored the receptor mediated transportion. The uptake of lanreotide-PM was found to be related to the expression level of SSTR2 in different cell lines and the competitive inhibition phenomenon indicated that the cellular uptake of lanreotide-PM was via a receptor meditated mechanism. In vivo, more lanreotide-PM accumulated in SSTR2 high expression tumor xenografts, endocytosed by the tumor cells, induced more apoptosis of tumor cells, and suppressed tumor growth efficiently. In conclusion, lanreotide-modified micelles containing antitumor drugs provide a promising strategy for the treatment of SSTR-expressing tumors.
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Kinase Regulation by Hydrophobic Spine Assembly in Cancer.
Mol. Cell. Biol.
PUBLISHED: 10-29-2014
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A new model of kinase regulation based on the assembly of hydrophobic spines has been proposed. Changes in their position can explain the mechanism of kinase activation. Here we examined mutations in human cancer for clues about the regulation of the hydrophobic spines by focusing initially on mutations to Phe. We identified a selected number of Phe mutations in a small group of kinases that included BRAF, ABL1, and EGFR. Testing some of these mutations in BRAF, we found that one of the mutations impaired ATP binding and catalytic activity but promoted non-catalytic allosteric functions. Other Phe mutations functioned to promote constitutive catalytic activity. One of these mutations revealed a previously underappreciated hydrophobic surface that functions to position the dynamic regulatory ?C-helix. This supports the key role of the C-helix as a signal integration motif for coordinating multiple elements of the kinase to create an active conformation. The importance of the hydrophobic space around the ?C-helix was further tested by a V600F mutant, which was constitutively active in the absence of the negative charge that is associated with the common V600E mutation. Many hydrophobic mutations strategically localized along the C-Helix can thus drive kinase activation.
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Computer aided quantification for retinal lesions in patients with moderate and severe non-proliferative diabetic retinopathy: a retrospective cohort study.
BMC Ophthalmol
PUBLISHED: 10-20-2014
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Detection of retinal lesions like micro-aneurysms and exudates are important for the clinical diagnosis of diabetes retinopathy. The traditional subjective judgments by clinicians are dependent on their experience and can be subject to lack of consistency and therefore a quantification method is worthwhile.
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Beneficial effects of pioglitazone on retardation of persistent atrial fibrillation progression in diabetes mellitus patients.
Int Heart J
PUBLISHED: 10-14-2014
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This study aimed to explore the effects of pioglitazone treatment on progression from persistent atrial fibrillation (AF) to permanent atrial fibrillation in diabetes mellitus (DM) patients and to investigate the possible mechanisms involved in those effects.A total of 146 diabetes mellitus (DM) patients with firstly identified persistent AF were selected. Seventy patients were randomized into the pioglitazone (30 mg/day) group and 76 into the placebo group. Pro-collagen type I carboxyterminal peptide (PICP), advanced glycation end products (AGEs), and angiotensin II were assayed and left atrial diameter (LA diameter) was measured at the first presence of persistent AF, and at 6 and 14 months of follow-up. The time point of identification of permanent AF and the incidence of permanent AF in the patients were all recorded.Thirty-seven (49%) of the 76 patients in the placebo group and 21 (30%) of the 70 patients in the pioglitazone group progressed to permanent AF (P = 0.028). No significant differences existed in the follow-up time (20.5 ± 3.97 months for pioglitazone group versus 20.9 ± 4.14 months for placebo group) between the two groups (P = 0.535). In the pioglitazone group, no significant change was found in angiotensin II level. The PICP level did not change significantly at 6-months of follow-up, but decreased significantly at 14-months of follow-up (P = 0.032). The AGE (P = 0.037 at 6-month follow-up, P < 0.035 at 14-month follow-up) level was significantly lower at both 6 and 14-months of followup.By lowering the PICP level, pioglitazone treatment may decrease the incidence of permanent AF in DM patients with persistent AF, which may be associated with the suppressing effect of pioglitazone on AGEs.
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A novel multiplexed fluorescence polarisation immunoassay based on a recombinant bi-specific single-chain diabody for simultaneous detection of fluoroquinolones and sulfonamides in milk.
Food Addit Contam Part A Chem Anal Control Expo Risk Assess
PUBLISHED: 10-14-2014
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Major research efforts are focusing on the development of simultaneous multiplexed immunoassays. In this study, a novel dual-binding fluorescence polarisation immunoassay (DB-FPIA) using a broad-specificity bi-specific single-chain diabody (scDb) and two fluorescent-labelled tracers (sulfamethoxypyridazine-fluorescein isothiocyanate (SMP-FITC) and sarafloxacin-Texas Red (SAR-TR)) with different excitation and emission wavelengths was developed for simultaneous and high-throughput detection of 19 fluoroquinolones (FQs) and 13 sulfonamides (SAs) at the maximum residue limits in milk samples. Recoveries for spiked milk samples were from 76.4% to 128.4%, with a relative standard deviation lower than 13.9%. The developed DB-FPIA was then applied to field samples, followed by confirmation by LC-MS/MS. All three instances in which FQs and SAs were present at concentrations near or above the assay limit of detection were identified as positive by the developed DB-FPIA, demonstrating that the method is suitable for rapid screening of FQs and SAs contamination. The novel methodology combines the advantage of the FPIA and the broad sensitivity of scDb and shows great promise for fast multi-analyte screening of low-molecular weight chemical residues in food samples.
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[Shenkang pill down-regulates AOPP-induced expression of inflammatory factor MCP-1 via a p38MAPK/NF-?B-dependent mechanism].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-30-2014
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To investigate the effect of the serum of rats fed with Shenkang pill in regulating monocyte chemoattractant protein 1 (MCP-1) expression induced by advanced oxidation protein products (AOPP) in mouse podocyte clone 5 (MPC5) and explore the underlying mechanism.
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A self-adaptive distance regularized level set evolution method for optical disk segmentation.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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The optic disc (OD) is one of the important anatomic structures on the retina, the changes of which shape and area may indicate disease processes, thus needs computerized quantification assistance. In this study, we proposed a self-adaptive distance regularized level set evolution method for OD segmentation without the periodically re-initializing steps in the level set function execution to a signed distance function during the evolution. In that framework, preprocessing of an image was performed using Fourier correlation coefficient filtering to obtain initial boundary as the beginning contour, then, an accurate boundary of the optic disc was obtained using the self-adaptive distance regularized level set evolution method. One hundred eye fundus color numerical images from public database were selected to validate our algorithm. Therefore, we believe that such automatic OD segmentation method could assist the ophthalmologist to segment OD more efficiently, which is of significance for future computer-aided early detection of glaucoma and retinopathy diseases.
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Examination of Huntington's disease in a Chinese family.
Neural Regen Res
PUBLISHED: 09-11-2014
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We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington's disease. Among 17 family members across three generations, four patients (II2, II6, III5, and III9) show typical Huntington's disease, involuntary dance-like movements. Magnetic resonance imaging found lateral ventricular atrophy in three members (II2, II6, and III5). Moreover, genetic analysis identified abnormally amplified CAG sequence repeats (> 40) in two members (III5 and III9). Among borderline cases, with clinical symptoms and brain imaging features of Huntington's disease, two cases were identified (II2 and II6), but shown by mutation analysis for CAG expansions in the important transcript 15 gene, to be non-Huntington's disease. Our findings suggest that clinical diagnosis of Huntington's disease requires a combination of clinical symptoms, radiological changes, and genetic diagnosis.
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Overexpression of FABP7 promotes cell growth and predicts poor prognosis of clear cell renal cell carcinoma.
Urol. Oncol.
PUBLISHED: 09-02-2014
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Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies; however, the molecular events supporting RCC carcinogenesis remain poorly understood. The aim of the present study was to determine the differential expression of genes between normal kidney and clear cell RCC (ccRCC) samples and investigate the biological function of the most frequently altered gene in RCC cells.
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Complete genomic sequence of the Vibrio alginolyticus lytic bacteriophage PVA1.
Arch. Virol.
PUBLISHED: 08-27-2014
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A novel Vibrio alginolyticus lytic bacteriophage was isolated from sewage samples obtained from a local aquatic market. Morphological analysis revealed that the phage, designated as PVA1, belonged to the family Podoviridae. The complete genomic sequence of phage PVA1 contained 41,529 bp with a G + C content of 43.7 % and 75 putative open reading frames. The genome was grouped into four modules, including phage structure, DNA packaging, DNA replication and regulation, and some additional functions. Further genomic comparison of the phage PVA1 with other known phages showed no significant similarities. Genes related to virulence and lysogeny were not detected in the phage genome. Our results suggest that phage PVA1 may be classified as a new Vibrio phage. We believe that these phage genomic sequence data will provide useful basic information for further molecular research on this Vibrio phage and its host as well for determining its infection/interaction mechanisms.
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Glycyrrhizin protects brain against ischemia-reperfusion injury in mice through HMGB1-TLR4-IL-17A signaling pathway.
Brain Res.
PUBLISHED: 08-08-2014
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High mobility group box 1 (HMGB1)-Toll-like receptor 4 (TLR4) signaling has been recently found to induce interleukin (IL)-17A secretion in drug-induced hepatitis and myocardial I/R injury. The purpose of this study is to evaluate whether HMGB1-TLR4 signaling could induce IL-17A secretion and lead to brain I/R injury. We also sought to investigate whether glycyrrhizin elucidated its neuroprotective effects through HMGB1-TLR4-IL-17A signaling pathway. Various biochemical estimations, neurological status, and assessment of cerebral infarct size were carried out 72h after middle cerebral artery occlusion (MCAO) stroke. Apoptotic cells were assessed using a terminal deoxynucleotidyl transferase, dUTP nick and labeling (TUNEL) kit. The expression of HMGB1, IL-17A, bcl-2, bax and cleaved caspase-3, were determined by Western blot assay. In the present study we found that glycyrrhizin significantly decreased HMGB1 protein expression. Glycyrrhizin markedly reduced whereas recombinant HMGB1 (rHMGB1) increased IL-17A expression. HMGB1 induced increase of IL-17A was significantly diminished in TLR4-mutant C3H/HeJ mice. Brain injury and neurological deficits were largely abrogated by glycyrrhizin or IL-17A knockout. In contrast, rHMGB1 or recombinant mouse IL-17A markedly increased I/R injury. However, rHMGB1 had no effects on infarct size and neurological deficits in Il17a(-/-) mice following brain I/R injury. In addition, IL-17A knockout mice significantly increased bcl-2 protein expression and had fewer apoptotic cells, whereas recombinant IL-17A-treated mice significantly increased bax and cleaved caspase-3 protein expression and had more apoptotic cells. Together these results indicate that glycyrrhizin has neuroprotective efficacy in the postischemic brain through HMGB1-TLR4-IL-17A signaling pathway.
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Calmodulin and PI(3,4,5)P? cooperatively bind to the Itk pleckstrin homology domain to promote efficient calcium signaling and IL-17A production.
Sci Signal
PUBLISHED: 08-07-2014
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Precise regulation of the kinetics and magnitude of Ca(2+) signaling enables this signal to mediate diverse responses, such as cell migration, differentiation, vesicular trafficking, and cell death. We showed that the Ca(2+)-binding protein calmodulin (CaM) acted in a positive feedback loop to potentiate Ca(2+) signaling downstream of the Tec kinase family member Itk. Using NMR (nuclear magnetic resonance), we mapped CaM binding to two loops adjacent to the lipid-binding pocket within the Itk pleckstrin homology (PH) domain. The Itk PH domain bound synergistically to Ca(2+)/CaM and the lipid phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], such that binding to Ca(2+)/CaM enhanced the binding to PI(3,4,5)P3 and vice versa. Disruption of CaM binding attenuated Itk recruitment to the membrane and diminished release of Ca(2+) from the endoplasmic reticulum. Moreover, disruption of this feedback loop abrogated Itk-dependent production of the proinflammatory cytokine IL-17A (interleukin-17A) by CD4(+) T cells. Additionally, we found that CaM associated with PH domains from other proteins, indicating that CaM may regulate other PH domain-containing proteins.
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Tuning Surface Microstructure and Gradient Property of Polymer by Photopolymerizable Polysiloxane-modified Nanogels.
RSC Adv
PUBLISHED: 07-22-2014
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This paper reports a series of photopolymerizable polysiloxane-modified nanogels for regulating surface microstructure and gradient property of polymers, which were synthesized by solution polymerization under different feed ratios of a methacrylate-modified polysiloxane, urethane dimethacrylate (UDMA) and isobornyl methacrylate (IBMA) in the presence of a thiol chain transfer agent. The nanogel structure and composition were characterized by proton nuclear magnetic resonance ((1)H-NMR), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscope (TEM), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). The dispersion of these nanogels in triethylene glycol dimethacrylate (TEGDMA) can reduce the onset and magnitude of shrinkage stress during polymerization without compromise to mechanical properties of the resulting polymers. Most importantly, as demonstrated by elemental analysis and X-ray photoelectron spectroscopy (XPS), the nanogels exhibit good self-floating ability in the monomer/polymer matrix and the increase of polysiloxane content in the nanogel can enhance the self-floating capability due to the lower surface tension and energy associated with the polysiloxane component. As a result, the polysiloxane-modified nanogels can spontaneously form a concentration gradient that can be locked in upon photopolymerization leading to a well-controlled heterogeneous polymer that presents a gradient change in thermal stability. With the increase of polysiloxane content, the thermal stability of the polymer was improved significantly. Furthermore, the enrichment of the nanogel on the surface resulting from the good self-floating ability can reduce the dispersion surface energy of gradient polymer film and generate a more hydrophobic surface with altered surface microstructure. These photopolymerizable polysiloxane-modified nanogels are demonstrated to have potential broad application in the preparation of gradient polymer with controlled surface properties.
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Felbamate as an add-on therapy for refractory epilepsy.
Cochrane Database Syst Rev
PUBLISHED: 07-19-2014
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This review is an update of a previously published review in The Cochrane Database of Systematic Reviews (Issue 1, 2011) on 'Felbamate as an add-on therapy for refractory epilepsy'. Epilepsy is a chronic and disabling neurologic disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available drugs. Felbamate is one of the second-generation antiepileptic drugs and its effects as an add-on therapy to standard drugs are assessed in this review.
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Photo-Reactive Nanogel as a Means to Tune Properties during Polymer Network Formation.
Polym Chem
PUBLISHED: 07-16-2014
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Photo-reactive nanogels with an integrated photoinitiator-based functionality were synthesized via a Reversible Addition-Fragmentation Chain Transfer (RAFT) process. Without additional free initiators, this nanogel is capable of radical generation and initiating polymerization of a secondary monomer (i.e. dimethacrylate) that infiltrates and disperses the nanogel particles. Due to the presence of RAFT functionality and the fact that all initiating sites are initially located within the nanogel structure, gelation can be delayed by sequencing the polymerization from the nanogel to the bulk matrix. During polymerization of a nanogel-filled resin system, a progressive delay of gelation conversion from about 2 % for conventional chain growth polymerization to 18 % for the same monomer containing 20 wt% nanogel additive was achieved. A significant delay of stress development was also observed with much lower final stress achieved with the nanogel-modified systems due to the change of network formation mechanics. Compared with the nanogel-free dimethacrylate control, which contained uniformly distributed free initiator, the flexural modulus and mechanical strength results were maintained for the photopolymers with nanogel contents greater than 10 wt%. There appears to be a critical interparticle spacing of the photo-reactive nanogel that provides effective photopolymerization while providing delayed gelation and substantial stress reduction.
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Charge separation in facet-engineered chalcogenide photocatalyst: a selective photocorrosion approach.
Nanoscale
PUBLISHED: 07-05-2014
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Finding active sites for photocatalytic reduction and oxidation allows the mechanistic understanding of a given reaction, ensuring the rational design and fabrication of an efficient photocatalyst. Herein, using well-shaped Cu2WS4 decahedra as model photocatalysts, we demonstrated that photoinduced oxidative etching could be considered as an indication of the photooxidation reaction sites of chalcogenide photocatalyst as it only occurred on {101} facets of Cu2WS4 during photocatalytic hydrogen production. The photocatalytic reduction reaction, in contrast, was confined on its {001} facets. Based on this finding, the photocatalytic activity of Cu2WS4 decahedra could be further tailored by controlling the ratio of {001}/{101} facets. Thus, this work provides a general route to the determination of reactive sites on shaped chalcogenide photocatalysts.
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Comprehensive characterization of cancer subtype associated long non-coding RNAs and their clinical implications.
Sci Rep
PUBLISHED: 06-30-2014
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Long non-coding RNAs (lncRNAs) are a kind of RNAs with regulation that participate fundamental cellular processes via diverse mechanisms. Despite the potential importance of lncRNAs in multiple kinds of cancer has been well studied, no comprehensive survey of cancer subtype associated lncRNAs. Here, we performed an array-based transcriptional survey of lncRNAs across 150 lung cancer samples comprising both adenocarcinoma and squamous cell carcinoma, and 306 breast cancer patients with clear clinical information. In lung cancer, 72 lncRNAs are identified to be associated with tumor subtypes and their functions as well as the associated proteins are predicted by constructing coding-non-coding co-expression network. The results suggest that they are mostly related with epidermis development, cell adhesion and response to stimulus. The validation results show the high concordance and confirmed the robust of the identification results. In breast cancer, we found 3 lncRNA genes are associated with estrogen receptor ? (ER) positive and ER negative subtypes and tumor histologic grade. Survival (Kaplan-Meier) analysis results suggest that the expression pattern of the 3 lncRNAs is significantly correlated with clinical outcomes. The current study provides the first large-scale survey of lncRNAs within cancer subtypes, and may offer new targets for their diagnosis, therapy and prognosis.
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Antimicrobial activity of the imipenem/rifampicin combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures.
World J. Microbiol. Biotechnol.
PUBLISHED: 06-18-2014
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To investigate the antimicrobial activity of imipenem and rifampicin alone and in combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures. Minimum inhibitory concentrations were determined for each isolate grown in suspension and in biofilm using a microbroth dilution method. Chequerboard assays and the agar disk diffusion assay were used to determine synergistic, indifferent or antagonistic interactions between imipenem and rifampicin. We used the tissue culture plate method for A. baumannii biofilm formation to measure the percentage of biofilm inhibition and the amount of extracellular DNA after the treatment. To understand the synergistic mechanisms, we conducted hydroxyl radical formation assays. The results were verified by confocal laser scanning microscopy. Imipenem and rifampicin showed effective antimicrobial activity against suspensions and biofilm cultures of A. baumannii, respectively. Synergistic antimicrobial effects between imipenem and rifampicin were observed in 13 and 17 of the 20 clinical isolates when in suspension and in biofilms, respectively. Imipenem and rifampicin alone and in combination generated hydroxyl radicals, which are highly reactive oxygen forms and the major components of bactericidal agents. Furthermore, treatment with imipenem and rifampicin individually or in combination has obvious antibiofilm effects. The synergistic activity of imipenem and rifampicin against clinical isolates of A. baumannii (in suspension and in biofilms) was observed in vitro. Therefore, we conclude that imipenem combined with rifampicin has the potential to be used as a combinatorial therapy for the treatment of infectious diseases caused by A. baumannii.
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Expression of bkt and bch genes from Haematococcus pluvialis in transgenic Chlamydomonas.
Sci China Life Sci
PUBLISHED: 06-16-2014
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?-carotene ketolase and ?-carotene hydroxylase encoded by bkt and bch, respectively, are key enzymes required for astaxanthin biosynthesis in Haematococcu pluvialis 34-1n. Two expression vectors containing cDNA sequences of bkt and bch were constructed and co-transformed into cell-wall-deficient Chlamydomonas reinhardtii CC-849. Transgenic algae were screened on TAP agar plates containing 10 ?g mL(-1) Zeomycin. PCR-Southern analysis showed that bkt and bch were integrated into the genomes of C. reinhardtii. Transcripts of bkt and bch were further confirmed by RT-PCR-Southern analysis. Compared with the wild type, transgenic algae produced 29.04% and 30.27% more carotenoids and xanthophylls, respectively. Moreover, the transgenic algae could accumulate 34% more astaxanthin than wild type. These results indicate that foreign bkt and bch genes were successfully translated into ?-carotene ketolase and ?-carotene hydroxylase, which were responsible for catalyzing the biosynthesis of astaxanthin in transgenic algae.
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Earth Surface Deformation in the North China Plain Detected by Joint Analysis of GRACE and GPS Data.
Sensors (Basel)
PUBLISHED: 06-14-2014
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Mass redistribution of the Earth causes variable loading that deforms the solid Earth. While most recent studies using geodetic techniques focus on regions (such as the Amazon basin and the Nepal Himalayas) with large seasonal deformation amplitudes on the order of 1-4 cm due to hydrologic loading, few such studies have been conducted on the regions where the seasonal deformation amplitude is half as large. Here, we use joint GPS and GRACE data to investigate the vertical deformation due to hydrologic loading in the North China Plain, where significant groundwater depletion has been reported. We found that the GPS- and GRACE-derived secular trends and seasonal signals are in good agreement, with an uplift magnitude of 1-2 mm/year and a correlation of 85.0%-98.5%, respectively. This uplift rate is consistent with groundwater depletion rate estimated from GRACE data and in-situ groundwater measurements from earlier report studies; whereas the seasonal hydrologic variation reflects human behavior of groundwater pumping for agriculture irrigation in spring, leading to less water storage in summer than that in the winter season. However, less than 20% of weighted root-mean-squared (WRMS) reductions were detected for all the selected GPS stations when GRACE-derived seasonal deformations were removed from detrended GPS height time series. This discrepancy is probably because the GRACE-derived seasonal signals are large-scale, while the GPS-derived signals are local point measurements.
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Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and antibody response.
J. Immunol.
PUBLISHED: 06-02-2014
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Lysophospholipids have emerged as biologically important chemoattractants capable of directing lymphocyte development, trafficking, and localization. Lysophosphatidic acid (LPA) is a major lysophospholipid found systemically, and its levels are elevated in certain pathological settings, such as cancer and infections. In this study, we demonstrate that BCR signal transduction by mature murine B cells is inhibited upon LPA engagement of the LPA5 (GPR92) receptor via a G?12/13-Arhgef1 pathway. The inhibition of BCR signaling by LPA5 manifests by impaired intracellular calcium store release and most likely by interfering with inositol 1,4,5-triphosphate receptor activity. We further show that LPA5 also limits Ag-specific induction of CD69 and CD86 expression and that LPA5-deficient B cells display enhanced Ab responses. Thus, these data show that LPA5 negatively regulates BCR signaling, B cell activation, and immune response. Our findings extend the influence of lysophospholipids on immune function and suggest that alterations in LPA levels likely influence adaptive humoral immunity.
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Localized nano-solid-solution induced by Cu doping in ZnS for efficient solar hydrogen generation.
Dalton Trans
PUBLISHED: 05-30-2014
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Nanosized photocatalysts have been shown to be important to many modern photocatalytic reactions. Control of the microstructure of the nanocrystals enables regulation of their optical properties and enhancement of specific reactions. Here, Cu(2+)-doped ZnS nanosphere photocatalysts with hierarchical nanostructures and controllable sizes were synthesized via a facile wet-chemical reaction. We demonstrated that small amounts of Cu(2+) doping could give rise to the formation of a variety of localized, nanosized Cu(1-x)Zn(x)S solid solutions that are separated by a continuous ZnS medium. The nano-solid-solutions have predictable band structures and an average size of several nanometers, which ensure facile generation of electron-hole pairs by visible light irradiation and quick migration of the photo-generated charges to the interfaces. With Ru as a cocatalyst, the as-prepared 0.5 mol% Cu(2+)-doped ZnS nanospheres showed a high H2 evolution rate of 1.03 mmol h(-1), corresponding to a quantum efficiency of 26.2% at 425 nm. A hierarchical surface structure with a large surface area is considered crucial for the increased activity. Our work not only showed that the non-toxic metal chalcogenides achieve high efficiency but also provides a new concept of localized nano-solid-solution for photocatalytic applications.
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[Value of postoperative radiochemotherapy for thoracic esophageal squamous cell carcinoma with lymph node metastasis].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 05-07-2014
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To retrospectively compare the efficacy of postoperative radiotherapy (RT) alone with that of postoperative radiotherapy with concurrent chemotherapy (CRT) for thoracic esophageal squamous cell carcinoma (EPC) with positive lymph nodes, and to evaluate the clinical value of RT + CRT.
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RAFT-mediated control of nanogel structure and reactivity: Chemical, physical and mechanical properties of monomer-dispersed nanogel compositions.
Dent Mater
PUBLISHED: 04-30-2014
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This study examines how nanogel structure correlates with photopolymerization and key polymer properties upon addition of nanogels with latent reactivity into a monomer dispersant to produce polymer/polymer composites.
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Recurrent primary lumbar vertebra chondrosarcoma: Marginal resection and Iodine-125 seed therapy.
Indian J Orthop
PUBLISHED: 04-18-2014
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Chondrosarcomas are uncommon in the spinal column. En bloc excisions with wide margins are of critical importance but not always feasible in spine. We report the outcome in a case of recurrent lumbar vertebral chondrosarcoma treated with marginal resection and iodine-125 seeds placed in the resected tumor bed.
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Outcome of single level anterior cervical discectomy and fusion using nano-hydroxyapatite/polyamide-66 cage.
Indian J Orthop
PUBLISHED: 04-18-2014
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Cages have been widely used for the anterior reconstruction and fusion of cervical spine. Nonmetal cages have become popular due to prominent stress shielding and high rate of subsidence of metallic cages. This study aims to assess fusion with n-HA/PA66 cage following one level anterior cervical discectomy.
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Mercury in the Canadian Arctic Terrestrial Environment: An Update.
Sci. Total Environ.
PUBLISHED: 04-09-2014
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Contaminants in the Canadian Arctic have been studied over the last twenty years under the guidance of the Northern Contaminants Program. This paper provides the current state of knowledge on mercury (Hg) in the Canadian Arctic terrestrial environment. Snow, ice, and soils on land are key reservoirs for atmospheric deposition and can become sources of Hg through the melting of terrestrial ice and snow and via soil erosion. In the Canadian Arctic, new data have been collected for snow and ice that provide more information on the net accumulation and storage of Hg in the cryosphere. Concentrations of total Hg (THg) in terrestrial snow are highly variable but on average, relatively low (<5ngL(-1)), and methylmercury (MeHg) levels in terrestrial snow are also generally low (<0.1ngL(-1)). On average, THg concentrations in snow on Canadian Arctic glaciers are much lower than those reported on terrestrial lowlands or sea ice. Hg in snow may be affected by photochemical exchanges with the atmosphere mediated by marine aerosols and halogens, and by post-depositional redistribution within the snow pack. Regional accumulation rates of THg in Canadian Arctic glaciers varied little during the past century but show evidence of an increasing north-to-south gradient. Temporal trends of THg in glacier cores indicate an abrupt increase in the early 1990s, possibly due to volcanic emissions, followed by more stable, but relatively elevated levels. Little information is available on Hg concentrations and processes in Arctic soils. Terrestrial Arctic wildlife typically have low levels of THg (<5?gg(-1) dry weight) in their tissues, although caribou (Rangifer tarandus) can have higher Hg because they consume large amounts of lichen. THg concentrations in the Yukon's Porcupine caribou herd vary among years but there has been no significant increase or decrease over the last two decades.
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[Effectiveness of nano-hydroxyapatite/polyamide 66 cage in anterior spinal reconstruction: a mid-term study].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 04-05-2014
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To evaluate the mid-term effectiveness of nano-hydroxyapatite/polyamide66 (n-HA/PA66) cage in the anterior spinal reconstruction.
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Electrophysiological and trafficking defects of the SCN5A T353I mutation in Brugada syndrome are rescued by alpha-allocryptopine.
Eur. J. Pharmacol.
PUBLISHED: 03-25-2014
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Brugada syndrome (BrS), which causes arrhythmias that lead to sudden cardiac death, is linked to loss-of-function mutations that affect sodium channels. Here, we investigate the rescue effect of alpha-allocryptopine (All) from Chinese herbal medicine in a T353I mutation of SCN5A, which combines trafficking abnormalities with Brugada syndrome. SCN5A-T353I expressed in HEK293 cells showed a small peak current (Ipeak) of only 59.6% of WT and an observably sustained current (Isus). We found that All strongly enhanced the Ipeak of the T353I channel by enhancing the plasma membrane (PM) expression of Nav1.5 and rescued defective trafficking after co-incubation with HEK293 cells that carry mutation channel 24h. It is also beneficial to increase the Ipeak of the T353I mutation by All by prolonging the closed-state inactivation (CSI) process and shortening the recovery from inactivation of the T353I mutation. Interestingly, the Isus of T353I was significantly inhibited by All, which reduces the occurrence of LQT syndrome 3 (LQT3). We provide evidence that All can rescue the trafficking deficiencies and restore the cellular electrophysiological characteristics of SCN5A-T353I. This feature of All may benefit patients with the BrS-associated Nav1.5 channel and might have other potential therapeutic effects.
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IL-17A contributes to brain ischemia reperfusion injury through calpain-TRPC6 pathway in mice.
Neuroscience
PUBLISHED: 03-23-2014
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Interleukin (IL)-17A plays an important role in the cerebral ischemia/reperfusion (I/R) injury. However, the mechanisms are still largely unknown. Calpain-transient receptor potential canonical (subtype) 6 (TRPC6) signaling pathway has been recently found to be implicated in brain I/R injury. However, their relationships with IL-17A remain unknown. This study aims to test whether this important signaling has correlation with IL-17A and how they led to the neuronal damage in I/R injury. In the present study, mice were subjected to middle cerebral artery occlusion (60 min) followed by reperfusion for different times. Infarct volumes and neurological deficits were examined. Real-time PCR (RT-PCR) and Western blotting were conducted to detect IL-17A expression in the penumbral brain tissue. Activation of calpain and expression of TRPC6 were also studied. We found that cerebral I/R significantly increased the levels of IL-17A at 1, 3 and 6 days after reperfusion in the penumbral area. IL-17A knockout or anti-IL-17A monoclonal antibody (mAb) significantly reduced whereas recombinant mouse-IL-17A (rIL-17A) increased the activation of calpain at 3 days after reperfusion. The calpain specific inhibitor calpeptin significantly increased TRPC6 expression. Brain injury and neurological deficits were largely abrogated by IL-17A knockout, anti-IL-17A mAb or calpeptin. Recombinant IL-17A treatment markedly increased I/R injury. In conclusion, IL-17A may promote brain I/R injury through the increase of calpain-mediated TRPC6 proteolysis. These results further outline a novel neuroprotective strategy with increased effectiveness for the inhibition of excess brain IL-17A in cerebral I/R injury.
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The effect of Lfcin-B on non-small cell lung cancer H460 cells is mediated by inhibiting VEGF expression and inducing apoptosis.
Arch. Pharm. Res.
PUBLISHED: 03-15-2014
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Lfcin-B, an antimicrobial peptide found in various exocrine secretions of mammals, showed antitumor effects. However, the effect and relative mechanism of Lfcin-B on non-small cell lung cancer is unclear. In this study, assay of cell viability, quantitative real-time PCR, Western blot, annexin V/propidium iodide assay, flow cytometry and tumor-xenograft model were applied to elucidate the mechanism of Lfcin-B on non-small cell lung cancer NCI-H460 (H460) cells. Lfcin-B significantly suppressed the proliferation of H460 cells in vitro. Additionally, the transcription and translation of the VEGF gene in H460 cells were restrained after exposure to Lfcin-B. Moreover, the apoptosis of H460 cells was induced by Lfcin-B through stimulating caspase-3, caspase-9 and preventing survivin expression on both the transcription and translation level. Meanwhile, Lfcin-B increased the production of reactive oxygen species and suppressed the RNA of antioxidant enzymes (GPX1, GPX2, SOD3 and catalase) in H460 cells. Finally, Lfcin-B significantly prevented the tumor growth in the H460-bearing mice model. These results indicated that Lfcin-B could be a potential candidate for the treatment of lung cancer.
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The impact of a chlorotoxin-modified liposome system on receptor MMP-2 and the receptor-associated protein ClC-3.
Biomaterials
PUBLISHED: 03-03-2014
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Currently, it is unknown whether a receptor-associated protein will be affected when a ligand modified delivery system interacts with its receptor. Besides, chlorotoxin (ClTx)-modified liposomes can target to glioma cells, but the target molecule is not clear: MMP-2, ClC-3 or both? Here a comparative study of ClTx-conjugated liposomes was conducted on two types of tumor cells: U87, a human glioma cell line with high expression of both MMP-2 and ClC-3, and A549, a human lung cancer cell line with expression of only MMP-2. ClTx-modified liposomes behaved similarly in these two cancer cells in terms of in vitro cell uptake, endocytosis pathway, intracellular trafficking and in vivo targeting efficacy, though the two tested cell lines were very different in ClC-3 expression. These results revealed that the targeted delivery of ClTx modified liposomes to U87 tumor was MMP-2-mediated and not correlated with the chloride channel ClC-3. On the other hand, ClTx modified on the liposomes did activate the receptor-associated protein ClC-3 via the binding with MMP-2, leading to the inhibition on cell migration and chloride currents. This is significant because cell migration is a key step in tumor metastasis. Interestingly, higher in vitro cellular uptake and lower in vivo tumor accumulation of liposomal systems was found in U87 compared to the A549 model, possibly due to the biological differences between in vitro and in vivo models. In general, ClTx-modified delivery systems may potentially target to tumors other than glioma that express a high level of MMP-2, and its effect on ClC-3 may help prevent tumor metastasis.
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Inhibition of metastatic tumor growth and metastasis via targeting metastatic breast cancer by chlorotoxin-modified liposomes.
Mol. Pharm.
PUBLISHED: 02-28-2014
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A liposome system modified with chlorotoxin (ClTx), a scorpion venom peptide previously utilized for targeting brain tumors, was established. Its targeting efficiency and antimetastasis behavior against metastatic breast cancer highly expressed MMP-2, the receptor of ClTx, were investigated. 4T1, a metastatic breast cancer cell line derived from a murine breast tumor, was selected as the cell model. As results, the ClTx-modified liposomes displayed specific binding to 4T1 as determined by flow cytometry and confocal imaging. The cytotoxicity assay revealed that the ClTx modification increased the toxicity compared with nonmodified liposomes. In addition, the modified liposomes also exhibited high in vivo targeting efficiency in the BALB/c mice bearing 4T1 tumors. Importantly, this system inhibited the growth of metastatic tumor and prevented the incidence of lung metastasis in mice bearing 4T1 tumors with only low systemic toxicity. The data obtained from the in vitro and in vivo studies confirmed that the ClTx-modified liposomes increased the drug delivery to metastatic breast cancers. This study proved that the ClTx-modified liposomes had targeting ability to metastatic breast cancer in addition to brain cancer, and displayed an obvious antimetastasis effect. Generally, it may provide a promising strategy for metastatic breast cancer therapy.
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Kinases and pseudokinases: lessons from RAF.
Mol. Cell. Biol.
PUBLISHED: 02-24-2014
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Protein kinases are thought to mediate their biological effects through their catalytic activity. The large number of pseudokinases in the kinome and an increasing appreciation that they have critical roles in signaling pathways, however, suggest that catalyzing protein phosphorylation may not be the only function of protein kinases. Using the principle of hydrophobic spine assembly, we interpret how kinases are capable of performing a dual function in signaling. Its first role is that of a signaling enzyme (classical kinases; canonical), while its second role is that of an allosteric activator of other kinases or as a scaffold protein for signaling in a manner that is independent of phosphoryl transfer (classical pseudokinases; noncanonical). As the hydrophobic spines are a conserved feature of the kinase domain itself, all kinases carry an inherent potential to play both roles in signaling. This review focuses on the recent lessons from the RAF kinases that effectively toggle between these roles and can be "frozen" by introducing mutations at their hydrophobic spines.
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Archives of total mercury reconstructed with ice and snow from Greenland and the Canadian High Arctic.
Sci. Total Environ.
PUBLISHED: 02-14-2014
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This study reports total Hg concentration and atmospheric flux data from ice cores and snow/ice shallow pits from two Canadian Arctic and one Greenland glaciers, with the aim of reconstructing a high resolution record of THg deposition extending back into the pre-industrial period. An 88-m ice core (653 samples) from the NEEM glacier site in Northwest Greenland was retrieved in August 2010. The bottom sample was dated to 1748, resulting in a 262year archive. Snow and ice samples (143 samples) were recovered from a 10.3-m pit dug on the Mt. Oxford Icefield, Nunavut, in May 2008, covering 30years. Another 15.5-m short core drilled on the Agassiz Ice Cap, Nunavut, in April 2009 yielded 191 samples covering 74years. Net rates of atmospheric THg deposition (FTHg) were calculated based on THg concentrations and snow accumulation rates. Results from NEEM site show that THg and FTHg range from sub-pg g(-1) to 120.6pgg(-1) (mean=1.5pgg(-1), n=653) and from 0.06 to 1.42?gm(-2) year(-1) (mean=0.25?gm(-2) year(-1), n=218) respectively, much lower than those found in other natural media such as sediments, peat bogs and wet precipitation. The discrepancy of FTHg found in glaciers from other natural media could mainly be due to the more severe photo-reduction and reemission of deposited oxidized Hg. This study also demonstrates that reproducible THg archives can be reconstructed with glacier ice and snow samples from Greenland and the Canadian High Arctic. The THg archive reconstructed with the short core from NEEM site is so far the longest with the highest resolution in Greenland and the Canadian High Arctic.
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Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity.
J Control Release
PUBLISHED: 02-12-2014
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As a sustained-release drug depot for localized cancer treatment, in situ thermo-sensitive hydrogel has attracted increasing interests. However, it is currently a big challenge to achieve high drug-loading, sustained and stable drug release, as well as long-term local drug retention simultaneously. We hypothesized that this goal could be accomplished by incorporating the nanocrystals (NCs) of a hydrophobic drug, such as paclitaxel (PTX) into the thermo-sensitive hydrogel (Gel). Hence, a PTX-NCs-Gel system has been constructed with thermo-sensitive Pluronic F127, using PTX-NCs and Taxol® as the controls. Besides, near infra-red agent DiR was used to prepare PTX/DiR hybrid NCs and PTX/DiR hybrid NCs-Gel as well. As a result, this hydrogel system could achieve a high drug loading of PTX up to 3 mg/ml while stabilize the particle size of PTX-NCs significantly compared with PTX-NCs alone. There was no obvious interaction between PTX-NCs and F127. Obviously, PTX/DiR hybrid NCs-Gel presented better localized retention capacity and a much longer retention time in murine 4T1 tumor than PTX/DiR hybrid NCs and Cremophor/ethanol solubilized DiR in vivo. With a linear elimination, over 10% of PTX still remained inside of mouse 4T1 tumor 20 days after intratumoral dosing of PTX-NCs-Gel. Importantly, PTX-NCs exhibited comparable cytotoxity against 4T1 and MCF-7 cells in vitro compared with Taxol®, which could ensure the efficacy of PTX-NCs-Gel. After intratumoral injection, PTX-NCs-Gel was found to be the most effective among all PTX formulations in the 4T1 and MCF-7 tumor-bearing mice models, with much lower system toxicity than Taxol®. In general, it is believed that the novel thermo-sensitive hydrogel system prepared in this study with PTX-NCs affords high drug-loading, sustained and stable drug release, as well as extended drug retention inside of tumor, which results in better therapy and lower toxicity.
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Targeting efficiency of RGD-modified nanocarriers with different ligand intervals in response to integrin ?v?3 clustering.
Biomaterials
PUBLISHED: 02-11-2014
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Receptor change induced by ligand binding is a new issue to face in the field of targeted delivery. Receptor clustering, the main pattern of receptor changes, decreases the affinity between ligand and receptor due to the redistribution of receptor position. In an attempt to respond to such challenge, we designed and constructed three RGD-modified nanocarriers with different ligand intervals: stealth liposomes modified with the monomeric RGD (moRGD-LP), dimeric RGD (diRGD-LP) and a special dimeric RGD with a linker between two cyclic RGD motifs (P-diRGD-LP). The ?v?3-positive and -negative tumor cells (Melanoma B16 and MCF-7) were used as the cell models. As a result, P-diRGD-LP demonstrated strongest interaction with B16 cells in surface plasmon resonance study and highest cellular uptake in B16 cells in real-time confocal analysis. The enhanced endocytosis of P-diRGD-LP was found to be ?v?3-mediated and P-diRGD-LP increased the involvement of the clathrin-dependent pathway. Importantly, P-diRGD-LP demonstrated the best targeting effect in B16-tumor bearing mice in both in vivo and ex vivo near-infrared fluorescent images, about 2.4-fold that of moRGD-LP and 2.8-fold that of diRGD-LP at 3 h. Further, we validated integrin ?v?3 clustering on B16 cells via a single-molecule imaging by a total internal reflection fluorescence microscopy. Finally, the 3D models of ?v?3 clustering suggested a receptor interval within 41.916-65.779 Å, while the molecular computation revealed an RGD ligand interval of 20.944 Å, 42.753 Å and 78.196 Å for diRGD-LP, P-diRGD-LP and moRGD-LP, respectively, confirming the best matching between clustered ?v?3 and P-diRGD-LP. In conclusion, P-diRGD-LP could achieve higher targeting to ?v?3-positive tumor via the enhanced interaction based on the better ligand-receptor compatibility. The design of targeted nanocarriers against receptor clustering might provide new insight into the nanotechnology-based anticancer therapy.
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Pd/activated carbon sorbents for mid-temperature capture of mercury from coal-derived fuel gas.
J Environ Sci (China)
PUBLISHED: 01-28-2014
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Higher concentrations of Hg can be emitted from coal pyrolysis or gasification than from coal combustion, especially elemental Hg. Highly efficient Hg removal technology from coal-derived fuel gas is thus of great importance. Based on the very excellent Hg removal ability of Pd and the high adsorption abilities of activated carbon (AC) for H?S and Hg, a series of Pd/AC sorbents was prepared by using pore volume impregnation, and their performance in capturing Hg and H?S from coal-derived fuel gas was investigated using a laboratory-scale fixed-bed reactor. The effects of loading amount, reaction temperature and reaction atmosphere on Hg removal from coal-derived fuel gas were studied. The sorbents were characterized by N? adsorption, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The results indicated that the efficiency of Hg removal increased with the increasing of Pd loading amount, but the effective utilization rate of the active component Pd decreased significantly at the same time. High temperature had a negative influence on the Hg removal. The efficiency of Hg removal in the N?-H?S-H?-CO-Hg atmosphere (simulated coal gas) was higher than that in N?-H?S-Hg and N?-Hg atmospheres, which showed that H? and CO, with their reducing capacity, could benefit promote the removal of Hg. The XPS results suggested that there were two different ways of capturing Hg over sorbents in N?-H?S-Hg and N?-Hg atmospheres.
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2'-hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis.
Oncol. Rep.
PUBLISHED: 01-28-2014
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Although there have been advances in therapeutic regimes for metastatic castration-resistant prostate cancer (CRPC), these recent developments have not led to improved cure rates. Thus, more novel agents to prolong patient survival are desired. 2'-Hydroxyflavanone (2HF), a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including prostate cancer (PCa). However, the therapeutic effects of 2HF on tumor growth and its potential mechanisms in CRPC have not been completely elucidated. In the present study, utilizing three different metastatic and androgen-independent PCa cell models (PC-3, DU145 and C4-2), we found that 2HF treatment not only resulted in inhibition of cell proliferation and colony formation in vitro, but also delayed subcutaneous tumor growth in vivo. Mechanistically, besides its known inhibitory effects on aldo?keto reductase activity and de novo androgen synthesis, 2HF also markedly suppressed AKT phosphorylation, signal transducer and activator of transcription-3 (STAT3) phosphorylation and transactivation subsequently regulating the expression of members of the BCL-2 family (i.e., Mcl-1, Bcl-2 and Bax) and modulating caspase-mediated cell apoptosis. Overall, this study revealed a novel mechanism for 2HF targeting metastatic CRPC, in which inactivation of AKT/STAT3 signaling led to cell apoptosis and growth inhibition.
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Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson's disease.
Neural Regen Res
PUBLISHED: 01-18-2014
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Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson's disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson's disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of ?-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson's disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson's disease by modulating neurotransmitter signaling in the corpus striatum.
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Ventricular septal rupture, right ventricular dissection, and tricuspid chordae rupture-A rare complication after inferior and right ventricular infarction.
J Clin Ultrasound
PUBLISHED: 01-10-2014
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A 76-year-old man under stable hemodynamic condition was admitted to our hospital for delayed percutaneous coronary intervention following a diagnosis of acute inferior myocardial infarction. Bedside echocardiography revealed ventricular septal rupture at the basal posteroinferior wall with a large left-to-right shunt. Right ventricular free-wall intramyocardial dissection and tricuspid chordae rupture were noted. Coronary angiography demonstrated occlusion of the proximal right coronary artery, which was treated by balloon angioplasty and stenting. While preparing for surgical repair, the patient's overall cardiac and renal function deteriorated and surgery was contraindicated. The patient died 16 days after discharge. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound, 2014.
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Improved peripheral nerve regeneration with sustained release nerve growth factor microspheres in small gap tubulization.
Am J Transl Res
PUBLISHED: 01-01-2014
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To evaluate the long-term results of the use of nerve growth factor (NGF)-loaded poly-D, L-lactide-co-glycolide (PLGA) microspheres for improve nerve regeneration with small gap tubulization.
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Identification and characterization of a novel HIV-1 circulating recombinant form (CRF59_01B) identified among men-who-have-sex-with-men in China.
PLoS ONE
PUBLISHED: 01-01-2014
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The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China. A large-scale national survey we conducted on HIV-1 strains among MSM in 11 provinces in China from 2008 to 2013 (n?=?920) identified a novel transmission cluster consisting of six strains (0.7%) that belonged to a new circulating recombinant form (designated CRF59_01B). CRF59_01B contains two subtype B segments of U.S.-European origin (in the pol and vpu-env regions) in a CRF01_AE backbone. CRF59_01B is the second CRF (after CRF55_01B) circulating primarily among MSM in China. CRF59_01B occurs at a low frequency (less than 1%), but it was detected in four different provinces/regions in China: Liaoning (northeast China) (n?=?3); Hunan (central China) (n?=?1); Guangdong (south China) (n?=?1); Yunnan (southwest China) (n?=?1). One additional recombinant strain was detected in a heterosexual individual in Liaoning province but is not the focus of this paper. Bayesian molecular clock analyses indicate that CRF59_01B emerged as a result of recombination between CRF01_AE and subtype B around the year 2001. The emergence of multiple forms of recombinants and CRFs reflects the ever-increasing contribution of homosexual transmission in China's HIV epidemic and indicates an active HIV transmission network among MSM in China.
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A strategy for finding the optimal scale of plant core collection based on Monte Carlo simulation.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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Core collection is an ideal resource for genome-wide association studies (GWAS). A subcore collection is a subset of a core collection. A strategy was proposed for finding the optimal sampling percentage on plant subcore collection based on Monte Carlo simulation. A cotton germplasm group of 168 accessions with 20 quantitative traits was used to construct subcore collections. Mixed linear model approach was used to eliminate environment effect and GE (genotype × environment) effect. Least distance stepwise sampling (LDSS) method combining 6 commonly used genetic distances and unweighted pair-group average (UPGMA) cluster method was adopted to construct subcore collections. Homogeneous population assessing method was adopted to assess the validity of 7 evaluating parameters of subcore collection. Monte Carlo simulation was conducted on the sampling percentage, the number of traits, and the evaluating parameters. A new method for "distilling free-form natural laws from experimental data" was adopted to find the best formula to determine the optimal sampling percentages. The results showed that coincidence rate of range (CR) was the most valid evaluating parameter and was suitable to serve as a threshold to find the optimal sampling percentage. The principal component analysis showed that subcore collections constructed by the optimal sampling percentages calculated by present strategy were well representative.
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Role of the stem cell-associated intermediate filament nestin in malignant proliferation of non-small cell lung cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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Nestin is associated with neoplastic transformation, but the mechanisms by which nestin contributes to invasion and malignancy of lung cancer remain unknown. Considering that proliferation is necessary for malignant behavior, we investigated the mechanism of nestin action in association with the proliferative properties of non-small cell lung cancer (NSCLC).
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Percutaneous endoscopic interlaminar discectomy for pediatric lumbar disc herniation.
Childs Nerv Syst
PUBLISHED: 01-01-2014
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Percutaneous endoscopic interlaminar discectomy (PEID) is a widely used minimally invasive procedure which shows satisfying outcomes in the adult population. However, pediatric lumbar disc herniations (PLDH) occur in growing spines and are less related to degeneration, which makes them different from the adult disc herniations. This study evaluates the clinical outcomes of PEID in treating PLDH.
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Hydrophobic penetrating peptide PFVYLI-modified stealth liposomes for doxorubicin delivery in breast cancer therapy.
Biomaterials
PUBLISHED: 11-14-2013
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Based on the hydrophobic interaction with biomembranes, PFVYLI (PFV), a hydrophobic penetration peptide (HPP), was initially introduced to modify doxorubicin-loaded stealth-sustained liposomes (PFV-SSLs-DOX) against different breast cancer cell phenotypes irrespective of their receptor expression or antigen presence. The physicochemical characteristics of PFV-SSLs were determined with approximately 100 nm size, satisfactory distribution and high encapsulation. In addition, drug release experiments demonstrated that modification with PFV has a negligible influence on the release profile of liposomes. Surface plasmon resonance (SPR) analysis revealed that PFV-modified liposomes could increase the binding proportion of PFV-SSLs with a model cell membrane. It was demonstrated that modification with PFV highly facilitated the intracellular delivery of DOX-loaded liposomes and enhanced cytotoxicity via a hydrophobic interaction. An endocytosis inhibition assay revealed a combination of cellular internalization mechanisms for PFV-SSLs involving lipid raft and clathrin-mediated endocytosis in a temperature-dependent manner. The PFV-modified liposomes displayed more lasting accumulation in the tumor and better tumor growth inhibition with relatively low systemic and cardiac toxicity. In conclusion, PFV-SSLs might be a promising delivery system for the delivery of different therapeutic or imaging agents to heterogeneous tumors. More significantly, this study provides a new perspective on developing HPP-modified drug delivery system for antitumor therapy.
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[Effects of parthenolide on high glucose-induced cell proliferation, NF-?B activation and MCP-1 expression in rat mesangial cells].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 10-23-2013
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To explore the effects of parthenolide (PTL) on high glucose-stimulated cell proliferation, NF-?B activation and monocyte chemoattractant protein-1 (MCP-1) expression in rat mesangial cells (MCs).
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[Novel artificial lamina for prevention of epidural adhesions after posterior cervical laminectomy].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 09-26-2013
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To evaluate the application of artificial lamina of multi-amino-acid copolymer (MAACP)/nano-hydroxyapatite (n-HA) in prevention of epidural adhesion and compression of scar tissue after posterior cervical laminectomy.
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[Morphologic study on rib regeneration in patients with adolescent idiopathic scoliosis after convex short length rib resection].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 09-26-2013
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To compare the rib regeneration in patients with adolescent idiopathic scoliosis (AIS) after convex short length rib resection or conventional thoracoplasty.
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Early (2008-2010) hospital outbreak of Klebsiella pneumoniae producing OXA-48 carbapenemase in the UK.
Int. J. Antimicrob. Agents
PUBLISHED: 08-28-2013
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OXA-48 ?-lactamase is one of the several emerging carbapenemases. Pre-2007 reports were almost exclusively from Turkey, but subsequently its distribution has expanded. We report an early and prolonged outbreak in the UK of Klebsiella pneumoniae producing OXA-48 carbapenemase affecting a predominantly renal cohort in a West London hospital. Carbapenemase production was detected by the modified Hodge test, with confirmation by PCR for blaOXA-48. Isolates were typed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Risk factors for acquisition were determined. Between January 2008 and April 2010, 20 K. pneumoniae isolates with reduced susceptibility to carbapenems were identified from 13 patients, comprising 12 renal cases and 1 oncology patient; 8 were outpatients and 5 were inpatients; 7 were deemed to be colonised and 6 infected, including 2 with bacteraemia, 1 of whom died. Hodge tests were positive for all isolates and all had blaOXA-48. PFGE showed strain similarity in isolates from nine patients, whereas four patients isolates were distinct, representing three further PFGE profiles and suggesting horizontal spread of blaOXA-48. Most patients had received antibiotics in the preceding 3 months and all had healthcare contact, but none had recent travel to areas with endemic OXA-48 Enterobacteriaceae. The renal cohort was screened and a prevalence rate of 0.17% was found. Interventions that collectively brought the outbreak under control included strict infection control precautions, screening, improved laboratory detection protocols and antibiotic stewardship rounds.
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Comparison of anterior cervical fusion by titanium mesh cage versus nano-hydroxyapatite/polyamide cage following single-level corpectomy.
Int Orthop
PUBLISHED: 08-19-2013
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The titanium mesh cage (TMC) is a typical metal cage device which has been widely used in cervical reconstruction for decades. Nano-hydroxyapatite/polyamide-66 (n-HA/PA66) cage is a novel biomimetic non-metal cage device growing in popularity in many medical centres in recent years. There has been no comparison of the efficacy between these two anterior reconstructing cages. The purpose of this study was to compare the radiographic and clinical outcomes of these two different devices.
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The clinical significance of HER-2 and NF-KB expression in gastric cancer.
Hepatogastroenterology
PUBLISHED: 08-13-2013
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To investigate the expression of human epidermal growth factor 2 (HER-2) and Nuclear factor-Kb (NF-KB) in gastric cancer, and the relation of these two parameters with stage, grade and metastasis of gastric cancer.
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Pseudokinases from a structural perspective.
Biochem. Soc. Trans.
PUBLISHED: 07-19-2013
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The catalytic (C) subunit of PKA was the first protein kinase structure to be solved, and it continues to serve as the prototype for the protein kinase superfamily. In contrast, by comparing many active and inactive kinases, we developed a novel spine concept where every active kinase is composed of two hydrophobic spines anchored to a hydrophobic F-helix. The R-spine (regulatory spine) is dynamically assembled, typically by activation loop phosphorylation, whereas the C-spine (catalytic spine) is completed by the adenine ring of ATP. In the present paper, we show how the spine concept can be applied to B-Raf, specifically to engineer a kinase-dead pseudokinase. To achieve this, we mutated one of the C-spine residues in the N-lobe (N-terminal lobe), Ala481, to phenylalanine. This mutant cannot bind ATP and is thus kinase-dead, presumably because the phenylalanine ring fills the adenine-binding pocket. The C-spine is thus fused. However, the A481F mutant is still capable of binding wild-type B-Raf and wild-type C-Raf, and dimerization with a wild-type Raf leads to downstream activation of MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] and ERK. The mutant requires dimerization, but is independent of Ras and does not require enzymatic activity. By distinguishing between catalytic and scaffold functions of B-Raf, we define kinases as being bifunctional and show that, at least in some cases, the scaffold function is sufficient for downstream signalling. Since this alanine residue is one of the most highly conserved residues in the kinome, we suggest that this may be a general strategy for engineering kinase-dead pseudokinases and exploring biological functions that are independent of catalysis.
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Analysis of serum and urinal copper and zinc in Chinese northeast population with the prediabetes or diabetes with and without complications.
Oxid Med Cell Longev
PUBLISHED: 07-15-2013
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This study investigated the association of copper and zinc levels in the serum or urine of patients living in northeast China, with either prediabetes or diabetes. From January 2010 to October 2011, patients with type 1 diabetes (T1D, n = 25), type 2 diabetes (T2D, n = 137), impaired fasting glucose (IFG, n = 12) or impaired glucose tolerance (IGT, n = 15), and age/gender matched controls (n = 50) were enrolled. In the T2D group, there were 24 patients with nephropathy, 34 with retinopathy, and 50 with peripheral neuropathy. Serum copper levels were significantly higher in IFG, IGT, and T2D groups. Serum zinc level was dramatically lower, and urinary zinc level was significantly higher in both T1D and T2D subjects compared with controls. The serum zinc/copper ratio was significantly lower in all the patients with IFG, ITG, T1D, and T2D. The serum copper level was positively associated with HbA1c in T2D subjects. Simvastatin treatment in T2D patients had no significant effect on serum and urinary copper and zinc. These results suggest the need for further studies of the potential impact of the imbalanced serum copper and zinc levels on metabolic syndrome, diabetes, and diabetic complications.
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Hemivertebrae resection for unbalanced multiple hemivertebrae: is it worth it?
Eur Spine J
PUBLISHED: 07-09-2013
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To assess the correction effect of hemivertebra resection for unbalanced multiple hemivertebrae by measuring corresponding parameters in both coronal and sagittal planes on series posteroanterior and lateral radiographs and report the related complications.
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Silibinin inhibits ?-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness.
Cell. Signal.
PUBLISHED: 07-09-2013
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Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including bladder cancer. Our and other previous studies have demonstrated that silibinin induced apoptosis and inhibited proliferation of bladder cancer cells, whether silibinin could suppress bladder cancer metastasis has not been elucidated. In the present study, we utilized a novel highly metastatic T24-L cell model, and found that silibinin treatment not only resulted in the suppression of cell migration and invasion in vitro, but also decreased bladder cancer lung metastasis and prolonged animal survival in vivo. Mechanistically, silibinin could inhibit glycogen synthase kinase-3? (GSK3?) phosphorylation, ?-catenin nuclear translocation and transactivation, and ZEB1 gene transcription that subsequently regulated the expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to reverse epithelial-mesenchymal transition (EMT). On the other hand, silibinin inhibited ZEB1 expression and then suppressed the properties of cancer stem cells (CSCs), which were evidenced as decreased spheroid colony formation, side population, and the expression of stem cell factor CD44. Overall, this study reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in which inactivation of ?-catenin/ZEB1 signaling by silibinin leads to dual-block of EMT and stemness.
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Total mercury in snow and ice samples from Canadian High Arctic ice caps and glaciers: A practical procedure and method for total Hg quantification at low pgg(-1) level.
Sci. Total Environ.
PUBLISHED: 06-25-2013
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A newly developed procedure and method for studying total Hg (THg) in the High Arctic glaciers and ice caps, including container type selection, on-site sampling, sample protection and storage, and sample decontamination is reported in this study. Two analytical systems for THg quantification were also compared to confirm the accuracy and reproducibility. This study found that container types, storage time, sample protection from exposure to light and environment are all important for precise quantification of THg in snow and ice samples from the Canadian High Arctic glaciers and ice caps. With this newly developed procedure and method, we retrieved 28-year and 73-year archives for atmospheric THg deposition from Mt. Oxford and Agassiz Ice Cap respectively. Our results show that snow and ice samples contain THg concentrations varying from sub pgg(-1) to low pgg(-1). Comparison of THg concentration trends and fluxes from the two sites demonstrates that quantification of THg from the two locations with similar altitudes and latitudes can be reproducible, which suggests that historical THg information from atmospheric deposition can be preserved in snow and ice in the glaciers and ice caps. The high reproducibility of results achieved by this procedure and method, in return, confirmed its suitability for studies of THg in snow and ice samples from ice caps and glaciers.
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[Application of reduction by posterior approach to treat severe spondylolisthesis].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 06-14-2013
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To investigate the technique of reduction by posterior approach for severe spondylolisthesis, and to discuss the method to prevent nerve stretch injury.
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[Effectiveness of posterior intrasegmental fixation with pedicle screw-lamina hook system in treatment of lumbar spondylolysis].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 05-16-2013
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To investigate the effectiveness of posterior intrasegmental fixation with pedicle screw-lamina hook system and bone grafting for lumbar spondylolysis.
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[Comparison of short-term effectiveness between minimally invasive surgery- and open-transforaminal lumbar interbody fusion for single-level lumbar degenerative disease].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 05-16-2013
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To compare the short-term effectiveness of minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF) versus open-TLIF in treatment of single-level lumbar degenerative disease.
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The cyclin D1 (CCND1) G870A polymorphism and lung cancer susceptibility: a meta-analysis.
Tumour Biol.
PUBLISHED: 04-19-2013
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Several studies have investigated the association between Cyclin D1 (CCND1) G870A genetic polymorphism and lung cancer susceptibility, but the results were inconclusive. The aim of this meta-analysis was to summarize available evidence for such a relationship. The reviewers made use of MEDLINE, EMBASE, and BIOSIS databases. The relevant data were independently extracted by two reviewers. The odds ratio (OR) with 95 % confidence interval (CI) was selected as the principal outcome measure. The heterogeneity test, the publication bias test, and the sensitivity analysis were performed. Overall, a total of 10 case-control studies were included. Our meta-analysis indicated that CCND1 G870A genetic polymorphism was a risk factor for lung cancer under homozygote model (OR?=?1.18; 95 % CI?=?1.02, 1.37), recessive model (OR?=?1.21; 95 % CI?=?1.03, 1.41), and allele model (OR?=?1.11; 95 % CI?=?1.02, 1.21). In the subgroup analysis by source of ethnicity, a statistical increase of lung cancer risk was found among Asian groups for allele model (OR?=?1.11; 95 % CI?=?1.01-1.22). The present meta-analysis suggests that CCND1 G870A polymorphism may be a risk factor for lung cancer. Besides, allele A may contribute to increased lung cancer risk.
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Role of GLI-1 in epidermal growth factor-induced invasiveness of ARCaPE prostate cancer cells.
Oncol. Rep.
PUBLISHED: 04-04-2013
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Epidermal growth factor (EGF) signaling and Hedgehog (HH) signaling are both involved in prostate cancer (PCa) progression, yet the mechanisms through which these two pathways are synergistically linked require elucidation. In the present study, we aimed to ascertain how EGF and the HH signaling transcription factor GLI-1 are linked in prostate cancer invasiveness. ARCaP human prostate cancer cells, which included ARCaPE and ARCaPM cells, were used as a model in the present study. The expression of EGF receptor (EGFR) and the HH signaling transcriptional factor GLI-1 were detected in ARCaPE cells by immunofluorescence, and the ARCaPE cells were treated with human recombinant EGF protein (hrEGF) for 4 consecutive days in vitro. Transwell invasion assays were performed in the ARCaPE cells following treatment with DMSO (vehicle control), hrEGF, GATN61 (GLI-1-specific inhibitor), hrEGF plus GANT61 and in the ARCaPM cells. The expression of phosphorylated extracellular signal regulated kinase (p-ERK), total ERK and GLI-1 was detected by western blotting in ARCaPE cells at different time-points following treatment with hrEGF. The expression of EGFR and GLI-1 was detected in ARCaPE cells, which exhibited a cobblestone-like morphology, while after treatment with hrEGF, the cell morphology was altered to a spindle-shaped mesenchymal cell morphology. Transwell invasion assays demonstrated that hrEGF dramatically enhanced the invasive capability of the ARCaPE cells (p<0.05). Additionally, western blot assay demonstrated that the expression levels of p-ERK and GLI-1 in ARCaPE cells increased in a time-dependent manner after treatment with hrEGF (p<0.05); however, the expression levels of total ERK in the cells remained relatively unchanged. It also demonstrated that the GLI-1 inhibitor GANT61 could reverse the enhanced invasive effect induced by EGF in ARCaPE cells (p<0.05). Our preliminary in vitro study showed that EGF signaling may increase the invasive capability of ARCaPE human prostate cancer cells via upregulation of p-ERK and the HH signaling transcriptional factor GLI-1. Additionally, this enhanced cell invasive effect was reversed by a GLI-1-specific inhibitor in vitro. Consequently, it indicates that both EGF and HH signaling are synergistically involved in the progression of human prostate cancer ARCaP cells, and GlI-1 may be one of the important effectors, which is activated by EGF downstream signaling, to promote the invasiveness of ARCaPE prostate cancer cells.
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Structural and luminescence properties of Y2-x GeMoO8 :REx (RE?=?Eu, Tb) phosphors.
Luminescence
PUBLISHED: 03-24-2013
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Y2-x GeMoO8 :REx (RE?=?Eu, Tb) phosphors were synthesized using a facile sol-gel method. The morphology and structure of the phosphors were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD); while their luminescent properties were investigated by photoluminescence (PL) spectrometry. Our results reveal that all of these Y2-x GeMoO8 :REx (RE?=?Eu, Tb) phosphors adopted the tetragonal phase, belonging to Scheelite (CaWO4 ) structure. The obtained YGeMoO8 :Eu phosphors exhibit a strong emission in the red light range which can be assigned to the (5) D0 ???(7) F2 transition of Eu(3+) when it is excited at 459 nm. Under 392 and 489 nm excitation, the YGeMoO8 :Tb phosphors present predominant green emission ((5) D4 ???(7) F5 ) at 540 nm. The highest emission of the phosphors can be achieved by adjusting the doping concentration to be 0.25 for Eu(3+) and 0.15 for Tb(3+) , respectively. The promising luminescence properties of these materials indicate that they can be potentially applied to white-light-emitting diodes. Copyright © 2013 John Wiley & Sons, Ltd.
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Novel biodegradable lamina for lamina repair and reconstruction.
Spine J
PUBLISHED: 03-18-2013
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Posterior laminectomy is an effective spinal surgical procedure. The adhesion of postoperative scar tissue to surgically exposed dura and, occasionally, to nerve roots can cause failed back surgery syndrome. The establishment of a barrier between scar tissue and dura that is made of hard material may prevent scar adhesions.
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An autoregulatory loop controlling Arabidopsis HsfA2 expression: role of heat shock-induced alternative splicing.
Plant Physiol.
PUBLISHED: 03-15-2013
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Heat shock transcription factorA2 (HsfA2) is a key regulator in response to heat stress in Arabidopsis (Arabidopsis thaliana), and its heat shock (HS)-induced transcription regulation has been extensively studied. Recently, alternative splicing, a critical posttranscriptional event, has been shown to regulate HS-inducible expression of HsfA2; however, the molecular mechanism remains largely unknown. Here, we demonstrate a new heat stress-induced splice variant, HsfA2-III, is involved in the self-regulation of HsfA2 transcription in Arabidopsis. HsfA2-III is generated through a cryptic 5 splice site in the intron, which is activated by severe heat (42°C-45°C). We confirmed that HsfA2-III encodes a small truncated HsfA2 isoform (S-HsfA2) by an immunoblot assay with anti-S-HsfA2 antiserum. S-HsfA2 has an extra leucine-rich motif next to its carboxyl-terminal truncated DNA-binding domain. The biological significance of S-HsfA2 was further demonstrated by its nuclear localization and heat shock element (HSE)-binding ability. In yeast (Saccharomyces cerevisiae), the leucine-rich motif can inhibit the transcriptional activation activity of S-HsfA2, while it appears not to be required for the truncated DNA-binding domain-mediated binding ability of S-HsfA2-HSE. Further results reveal that S-HsfA2 could bind to the TATA box-proximal clusters of HSE in the HsfA2 promoter to activate its own transcription. This S-HsfA2-modulated HsfA2 transcription is not mediated through homodimer or heterodimer formation with HsfA1d or HsfA1e, which are known transcriptional activators of HsfA2. Altogether, our findings provide new insights into how HS posttranscriptionally regulates HsfA2 expression. Severe HS-induced alternative splicing also occurs in four other HS-inducible Arabidopsis Hsf genes, suggesting that it is a common feature among Arabidopsis Hsfs.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.