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Find video protocols related to scientific articles indexed in Pubmed.
Field-Induced Slow Magnetic Relaxation in Cobalt(II) Compounds with Pentagonal Bipyramid Geometry.
Inorg Chem
PUBLISHED: 11-20-2014
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Field-induced slow magnetic relaxation was observed for air-stable mononuclear cobalt(II) compounds with pentagonal bipyramid geometry. These are the first examples of such behavior observed in the seven-coordinated mononuclear 3d metal compounds.
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In vitro Immunomodulatory Activity of Oxymatrine on Toll-Like Receptor 9 Signal Pathway in Chronic Hepatitis B.
Am. J. Chin. Med.
PUBLISHED: 11-20-2014
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Oxymatrine, extracted from the herb Sophora alopecuraides L., was investigated to determine its anti-HBV immunomodulatory mechanism in vitro. Human peripheral lymphocytes were isolated from heparinized whole blood from 48 chronic hepatitis B (CHB) patients. The lymphocytes from each patient were divided into two groups according to pretreatment or no pretreatment with Oxymatrine in vitro. We examined the changes of expression and function of the toll-like receptor 9 (TLR9) signal transduction pathway in the peripheral lymphocytes with different treatment methods and investigated the synergism of Oxymatrine and the TLR9 ligand on antiviral cytokine secretions in vitro. The data showed Oxymatrine could induce antiviral cytokine secretions directly from the peripheral lymphocytes. For the TLR9 signal pathway, Oxymatrine not only augmented the expressions of TLR9 signal transduction molecules, but also activated the TLR9 signal function. This study has clearly demonstrated that TLR9 ligand could stimulate peripheral lymphocytes that have been pretreated with Oxymatrine. Furthermore, the quantity of antiviral cytokines secreted by the pretreated lymphocytes was greater than that of those without pretreatment. The interaction between the Oxymatrine and the TLR9 ligand appears to be synergistic. This study suggests Oxymatrine could be a strong immunomodulator, influence TLR9 signaling transduction, and synergistically improve the immune efficacy of the TLR9 ligand against CHB.
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Enhancement of fluorescence molecular tomography with structural-prior-based diffuse optical tomography: combating optical background uncertainty.
Appl Opt
PUBLISHED: 11-18-2014
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The common approach in fluorescence molecular tomography (FMT) assumes homogeneous distributions of the optical properties and normally results in reconstructions of low sensitivity. A natural enhancement is to incorporate diffuse optical tomography (DOT) to FMT. However, the traditional voxel-based DOT has been a severely ill-posed inverse problem and cannot retrieve the optical property distributions accurately. We present a structural-prior-based DOT method to effectively acquire the heterogeneous optical background with the aid of some imperfect structural priors from x-ray computed tomography and/or magnetic resonance imaging anatomical imaging modalities, and quantitatively compare its hard- and soft-prior schemes for achieving an improved recovery of the fluorescence distribution. Numerical simulations are conducted on a region-labeled three-dimensional (3D) digital mouse model to investigate the performance of this method. Physical experiments on a cylindrical phantom are also conducted to assess this methodology. Our simulated and experimental reconstruction results indicate that the structural-prior-based DOT guided FMT approach can significantly improve the sensitivity of FMT reconstruction, as well as its imaging resolution and quantitative accuracy.
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Design of a hybrid As2S3-Ti:LiNbO3 optical waveguide for phase-matched difference frequency generation at mid-infrared.
Opt Express
PUBLISHED: 11-18-2014
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Based on arsenic tri-sulfide films on titanium-diffused lithium niobate, we designed a hybrid optical waveguide for efficient mid-infrared emission by phase-matched difference frequency generation (DFG). The hybrid waveguide structure possesses a low-index magnesium fluoride buffer layer sandwiched between two high-index As2S3 slabs, so that pump and signal waves are tightly confined by titanium-diffused waveguide while the DFG output idler wave at mid-infrared is confined by the whole hybrid waveguide structure. On a 1 mm-long hybrid waveguide pumped at 50 mW powers, a normalized power conversion efficiency of 20.52%W-1cm-2 was theoretically predicted, which is the highest record for mid-infrared DFG waveguides based on lithium niobate crystal, to the best of our knowledge. Using a tunable near-infrared pump laser at 1.38-1.47 µm or a tunable signal laser at 1.95-2.15 µm, a broad mid-infrared tuning range from 4.0 µm to 4.9 µm can be achieved. Such hybrid optical waveguides are feasible for mid-infrared emission with mW powers and sub-nanometer linewidths.
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Immunosuppressive treatment combined with nucleoside analog is superior to nucleoside analog only in the treatment of severe thrombocytopenia in patients with cirrhosis associated with hepatitis B in China: A multicenter, observational study.
Platelets
PUBLISHED: 11-15-2014
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Abstract No effective treatment has been identified for patients of liver cirrhosis (LC) associated with hepatitis B virus (HBV) and severe thrombocytopenia. We aimed to explore the effectiveness and safety of low-dose prednisone or cyclosporine A (CsA) combined with nucleoside analog (NA) in patients with severe thrombocytopenia associated with HBV-related LC. We included 145 consecutive compensated HBV-associated LC patients with severe thrombocytopenia between 1 January 2006 and 31 December 2013. We divided the patients into three groups by treatment strategy, including NA only (n?=?57), NA plus prednisone (n?=?46), and NA plus CsA (n?=?42). We analyzed the platelet counts, bleeding events, liver function, replication of HBV, and outcomes in each group. At all time points during this observation, the platelet counts in prednisone or CsA group were higher than those in the NA only group. There are significant differences in the cumulative rates of bleeding events among the three groups. The platelet counts and treatment were factors associated with bleeding events in multivariate analysis. The differences in HBV-DNA negative rates, HBV-DNA elevated rates, normal serum alanine transaminase rates, serum alanine transaminase elevated more than two times the baseline rates, and HBeAg seropositive conversion ratio among the groups did not reach statistical significance. The adverse events in our study were, in general, mild and balanced among the three treatment groups. Treatment with low-dose prednisone or CsA plus NA could elevate the platelet counts and reduce the risk of bleeding events in HBV LC with severe thrombocytopenia.
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Simultaneous Bilateral Video-Assisted Thoracoscopic Surgery for the Treatment of Primary Spontaneous Pneumothorax.
Cell Biochem. Biophys.
PUBLISHED: 11-14-2014
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We determined the feasibility and clinical efficacy of simultaneous bilateral video-assisted thoracoscopic surgery (VATS) for treating primary spontaneous pneumothorax (PSP). We performed a retrospective analysis of the efficacy of simultaneous bilateral resection of pulmonary bullae using VATS in 21 PSP patients that were treated at our hospital from February 2010 to August 2013. We found bilateral bullae in all patients through the intraoperative exploration. Surgical procedures were successfully completed in all patients without conversion to thoracotomy. The mean time of surgery was 128.76 ± 13.82 min (range 100-150 min). Total amount of intraoperative bleeding was 80-200 ml. Total drainage of bilateral thoracic ducts was 200-500 ml at the 1st postoperative day with a mean drainage of 321.42 ± 82.66 ml. Bilateral thoracic ducts were removed 4-8 days postoperatively with a mean time of 4.7 days. The duration of postoperative hospitalization was 5-9 days with a mean duration of 7 days. No patient had serious complication(s) and all patients were discharged after full recovery. The patients were followed up for 6-18 months after the surgery and no relapse occurred. In conclusion, treating the unilateral PSP by simultaneous bilateral VATS is safe and effective. It reduces patients' risk of second surgery and also minimizes patients' suffering and costs incurred.
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Foretinib is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma.
Cancer Res.
PUBLISHED: 11-14-2014
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Medulloblastoma is the most common malignant pediatric brain tumor, with metastases present at diagnosis conferring a poor prognosis. Mechanisms of dissemination are poorly understood and metastatic lesions are genetically divergent from the matched primary tumor. Effective and less toxic therapies that target both compartments have yet to be identified. Here we report that the analysis of several large non-overlapping cohorts of medulloblastoma patients reveal MET kinase as a marker of sonic hedgehog (SHH) driven medulloblastoma. Immunohistochemical analysis of phosphorylated, active MET kinase in an independent patient cohort confirmed its correlation with increased tumor relapse and poor survival, suggesting that SHH medulloblastoma patients may benefit from MET-targeted therapy. In support of this hypothesis, we found that the approved MET inhibitor foretinib could suppress MET activation, decrease tumor cell proliferation and induce apoptosis in SHH medulloblastomas in vitro and in vivo. Foretinib penetrated the blood-brain barrier and was effective in both the primary and metastatic tumor compartments. In established mouse xenograft or transgenic models of metastatic SHH medulloblastoma, foretinib administration reduced the growth of the primary tumor, decreased the incidence of metastases and increased host survival. Taken together, our results provide a strong rationale to clinically evaluate foretinib as an effective therapy for patients with SHH-driven medulloblastoma.
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Making pyrophosphate visible: the first precipitable and real-time fluorescent sensor for pyrophosphate in aqueous solution.
Analyst
PUBLISHED: 11-11-2014
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An in situ generated BINOL-DPA-Zn(ii) complex is presented as a chemo-sensing ensemble for the recognition of phosphate-based molecules. The ensemble showed high sensitivity and selectivity for pyrophosphates (PPi), and it could be successfully applied in imaging PPi in living cells. Notably, the ensemble exhibited a very low detection limit (95 nM) for PPi and could realize the real time detection of PPi by the naked eye through precipitate experiments. The ensemble also showed good selectivity towards ATP, and the selectivity coefficient for PPi and ATP was calculated to be 4.1/2.8.
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First-principles study of ground-state properties of U2Mo.
Phys Chem Chem Phys
PUBLISHED: 11-07-2014
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By means of first-principles calculations, we have systematically investigated the structural, elastic, vibrational, thermal and electronic properties of the ground-state phase for the intermetallic compound U2Mo. Our results reveal that the previously synthesized I4/mmm structure of U2Mo is a metastable phase and unstable, neither thermodynamically nor vibrationally at the ground state. In combination with the evolutionary structural searches, our first-principles calculations suggest a new ground-state Pmmn phase, which has been confirmed theoretically to be stable, both thermodynamically and vibrationally. Moreover, through the DFT + D technique we have discussed the influence of van der Waals interactions on the structural, elastic and vibrational properties, revealing a weak effect in pure U and Mo solids and U2Mo alloy. The analysis of the electronic band structures evidences its electronic stabilities with the appearance of a deep valley in the density of states at the Fermi level. Moreover, we have investigated further the temperature-dependent structural, thermal expansion and elastic properties of our proposed Pmmn ground-state phase. These results are expected to stimulate further experimental investigations of the ground-state phase of U2Mo.
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Theoretical insights into nucleation of CO2 and CH4 hydrates for CO2 capture and storage.
Phys Chem Chem Phys
PUBLISHED: 11-07-2014
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We present a hybrid three-dimensional (3D) theoretical approach, the density functional theory (DFT) integrated with the reference interaction site model (RISM), to investigate the nucleation of CO2 and CH4 hydrates. Within the theoretical framework, the 3D-RISM is applied to describe gas density distributions in hydrate cages, and the 3D-DFT is used to describe the interfacial structure and properties of the two hydrates, as well as their nucleation. The crystal-liquid phase equilibria of CO2 and CH4 hydrates are predicted by the hybrid 3D-DFT-RISM, and compared with the available experimental data to examine the theoretical model. In particular, the local and interfacial structure and properties, the critical nucleus radii and free-energy barriers at moderate concentration supersaturation are presented to analyze their nucleation. The formation enthalpies for the two hydrates are calculated to evaluate the possibility of CO2 storage by CH4-CO2 replacement in hydrate.
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A 3D MOF showing unprecedented solvent-induced single-crystal-to-single-crystal transformation and excellent CO2 adsorption selectivity at room temperature.
Chem. Commun. (Camb.)
PUBLISHED: 11-07-2014
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A water stable porous 3D metal-organic framework, [Cu3L2(?3-OH)2(?2-H2O)]·2DMA (1, mother crystal, H2L = 2,2'-dinitrobiphenyl-4,4'-dicarboxylic acid, DMA = N,N-dimethylacetamide), shows unprecedented irreversible solvent-induced substitutions of bridging aqua ligands and guest-exchanges in single-crystal-to-single-crystal (SCSC) transformations at room temperature (RT), producing quantitatively three daughter crystals, [Cu3L2(?3-OH)2]·2S (2: 2A, S = acetone; 2B, S = 2-propanol; 2C, S = 2-butanol), which exhibit reversible interconversion by guest-exchanges at RT in SCSC transformations. MOF 1 shows excellent separation selectivity (128) of CO2/N2 at RT and is a better sorbent of micro-solid-phase extraction (?-SPE) than currently known benchmark ZIF-8.
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Overview of research on Bombyx mori microRNA.
J. Insect Sci.
PUBLISHED: 11-05-2014
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MicroRNAs (miRNAs) constitute some of the most significant regulatory factors involved at the post-transcriptional level after gene expression, contributing to the modulation of a large number of physiological processes such as development, metabolism, and disease occurrence. This review comprehensively and retrospectively explores the literature investigating silkworm, Bombyx mori L. (Lepidoptera: Bombicidae), miRNAs published to date, including discovery, identification, expression profiling analysis, target gene prediction, and the functional analysis of both miRNAs and their targets. It may provide experimental considerations and approaches for future study of miRNAs and benefit elucidation of the mechanisms of miRNAs involved in silkworm developmental processes and intracellular activities of other unknown non-coding RNAs.
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Adsorption of Lysozyme on Silver and Its Influence on Silver Release.
Langmuir
PUBLISHED: 11-04-2014
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Silver is increasingly used in antimicrobial coatings of biomedical devices and implants to hinder infections. As proteins have been shown to largely influence the extent of released metals from various metal surfaces at biological conditions, silver may also be influenced in the same way. The aim of this study is to relate the structure of adsorbed lysozyme (LSZ) to the release of silver from metallic silver surfaces. Simultaneous adsorption measurements were performed in real time on the same surface using combined ellipsometry and quartz crystal microbalance with dissipation monitoring measurements to provide a more comprehensive understanding on the adsorption kinetics and the layer structures. The concentration of LSZ in 0.15 M NaNO3 solution (pH 7, 25 °C) influences the structure of the adsorbed layer. Monolayer coverage is obtained at concentrations ?0.1 g/L, while a bilayer structure with a rigid inner layer and a relatively loosely adsorbed outer layer is formed at 1 g/L. The inner layer of LSZ is assumed to bind firmly to silver via disulfide bridges, which makes it irreversibly adsorbed with respect to dilution. The amount of released silver is further influenced by the structure of the LSZ layer. At low LSZ concentrations (?0.1 g/L) the amount of released silver is not significantly different compared with non-protein-containing NaNO3 solutions; however, noticeable reduction was observed at higher concentrations (1 g/L). This reduction in silver release has several possible explanations, including (i) surface complexation between LSZ and silver ions that may result in the incorporation of silver in the irreversible adsorbed layer and, hence, reduce the amount of released silver into solution, and (ii) net charge reversal at the protein/solution interface to slightly positive surface potentials. Any release of silver will therefore exhibit an electrostatic repulsion during transportation through the protein layer results in a reduced amount of silver in solution.
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PCR-Based National Bacterial Meningitis Surveillance in Turkey: Years 2006 to 2009.
Pediatr. Infect. Dis. J.
PUBLISHED: 11-01-2014
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Polymerase chain reaction-based surveillance for bacterial meningitis including 841 children revealed 246 with bacterial DNA in cerebrospinal fluid samples of which 53% were Streptococcus pneumoniae, 19% Neisseria meningitidis, and 16% Haemophilus influenzae type b. The most common S. pneumoniae serotypes/serogroups were 1, 19F, 6A/6B, 23F, 5, 14, 18 and 19A. Among 47 meningococci, 86% were serogroup B, 6% serogroup C, 3% serogroup A, 3% serogroup X and 3% serogroup W.
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Design and Optimization of Novel Hydroxamate-Based Histone Deacetylase Inhibitors of Bis-Substituted Aromatic Amides Bearing Potent Activities against Tumor Growth and Metastasis.
J. Med. Chem.
PUBLISHED: 11-01-2014
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Histone deacetylases (HDACs) are one of the most promising drug targets for cancer therapy, and since more than 90% of all cancer-related deaths are associated with tumor metastasis, developing strategies to inhibit tumor metastasis while retaining anti-tumor growth activity are of great interest. Herein we demonstrated the design and identification of a series of novel hydroxamate-based HDAC inhibitors bearing potent activities against tumor growth and metastasis. Optimization of the initial hit resulted in the discovery of new HDAC inhibitors through studying the structure-activity relationship. Among them, compound 11b, one of the most potent leads, exhibited nanomolar IC50 values toward inhibition of class I and IIb HDACs as well as sub-micromolar activity against proliferation and migration of breast cancer cells in vitro. More importantly, it also significantly suppressed tumor growth in a breast tumor xenograft mouse model and dose-dependently blocked in vivo tumor metastasis in a mouse pulmonary metastasis model.
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[Laser and vision measurement research on parameters of miniature quartz plate-sensitive glass part].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 11-01-2014
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High-precision, rapid and non-contact geometry parameter measurements of plate glass parts has become a main problem in the field of testing-related production and processing and also an important applied direction for laser spectroscopy. Accurately detect the geometric parameters of plate glass parts can not only improve the processing technology and the precision of assembly, but also bring about sub-file management according to the parameters. This paper presents a novel multi-parameter measurement method based on the laser and vision image processing technology, which can be used to measure parameters of miniature quartz plate-sensitive glass part accurately. The testing system consisting of self-adaption coaxial visual detection unit and laser vision thickness inspection unit was designed. A constant power drive control system was set up to ensure the laser diode (LD) can provide a stable light source for the testing system. A modified sub-pixel edge position algorithm of conic features was proposed to implement the sub-pixel image processing, and the parameters can be extracted. According to the data detected from curve edge points and a new-defined error function, which was minimized, the parameters of miniature quartz plate-sensitive glass part can be calculated. The experiments show that the average deviation of the measurement results is less than 2 ?m, and the method has good stability and high accuracy measurement, which can meet the precision requirement of parameter measurement for miniature plate glass part.
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[Expression of nesfatin-1/NUCB2 and ghrelin in gastric mucosa of rats with intrauterine growth retardation].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 10-26-2014
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To investigate the expression of nesfatin-1/NUCB2 and ghrelin in the gastric mucosa of rats with intrauterine growth retardation (IUGR) and its significance.
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8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations.
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[Research Progress on microRNA Associated with Chemoresistance of NHL].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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Non-Hodgkin's lymphoma (NHL) is a malignant tumor originated in lymphatic hematopoietic tissue. At present, chemotherapy is the main treatment method of NHL, but the chemoresistance is still an important reason for NHL treatment failure. The mechanism of NHL multidrug resistance (MDR) is complex, involving a variety of singnal pathways, in which mutation in the genetic level of the key genes can result in tumor cell resistance phenomenon. MicroRNA are small non-coding RNA that can be widely detected in plants,animal species and viruses. They regulate protein expression by repressing translation mRNA target at the post-transcriptional level, participating in the differentiation and development of tumor cells, as well as the occurrence and development of tumor, the change of the expression level microRNA plays an important role in the genesis and chemoresistance mechanism of NHL. Therefore, the intervening factitiously the expression level of microRNA in NHL through manufacturing antisense oligonucleotide (AMO) or using substitution of microRNA, changing the expression level of their target protein, and combining with the therapy of NHL, there will be an guiding significance in reversing the drug and radiation resistance of NHL, thus improving its poor prognosis. This article reviews the microRNAs closely related with drug and radiation resistance of NHL, and their potential targets. Furthermore, the specific role of these microRNAs in the genesis and chemoresistance mechanism of NHL are deeply elaborated.
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Structural Insights into the C1q Domain of Caprin-2 in Canonical Wnt Signaling.
J. Biol. Chem.
PUBLISHED: 10-22-2014
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Previously, we have identified Caprin-2 as a new regulator in canonical Wnt signaling through a mechanism of facilitating LRP5/6 phosphorylation; moreover, we found that its C-terminal C1q-related domain (Cap2_CRD) is required for this process. Here, we determined the crystal structures of Cap2_CRD from human and zebrafish, which both associate as a homotrimer with calcium located at the symmetric center. Surprisingly, the calcium- binding-deficient mutant exists as a more stable trimer than its wild-type counterpart. Further studies showed that this Caprin-2 mutant disabled in binding calcium maintains the activity of promoting LRP5/6 phosphorylation; while the mutations disrupting Cap2_CRD homotrimer did impair such activity. Together, our findings suggested that the C-terminal CRD domain of Caprin-2 forms a flexible homotrimer mediated by calcium; and that such trimeric assembly is required for Caprin-2 to regulate canonical Wnt signaling.
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[Functional connectivity in ischemia stroke motor aphasia patients during resting state].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-21-2014
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To investigate the changes of Broca's area functional connectivity in ischemia stroke patients with motor aphasia during resting state using functional magnetic resonance imaging (fMRI).
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Appositional Angle Closure in Chinese with Primary Angle Closure and Primary Angle Closure Glaucoma after Laser Peripheral Iridotomy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-18-2014
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Purpose: To determine the prevalence of appositional angle closure (AAC) after laser peripheral iridotomy(LPI) in the eyes of Chinese patients with primary angle closure (PAC) and primary angle closure glaucoma(PACG), and to evaluate its pathogenesis by investigating anatomic characteristics. Methods: This was a cross-sectional observational study. PAC and PACG subjects after LPI were consecutively enrolled. UBM image in darkness of each quadrant without peripheral anterior synechia (PAS) under gonioscopy was qualitatively assessed. Darkroom provocative test (DRPT) was also performed. Results: One hundred and thirty-four eyes of 134 patients were enrolled. AAC was observed in ?1 quadrant of UBM image in 85 subjects (63.4%). There were 116 (86.6%) randomly selected quadrants without PAS for 134 patients. AAC existed in 38 quadrants (32.8%).Among these, plateau iris accounted for 44.7%, anteriorly inserted iris for 13.2%, thick iris for 13.2%, and anteriorly inserted iris combined with thick iris for 18.4% of the total. One hundred and fifteen subjects underwent DRPT and its positive rate of eyes with AAC ? 2 quadrants (37.5%, 12/32) was significantly higher than those? 1quadrant (16.9%, 14/83)(p=0.018).However, no significant difference was found between eyes with non- synechia plateau iris ? 2 quadrants (36.4%, 4/11) and those ? 1 quadrant (21.2%, 22/104) (p=0.266). Conclusions: About two thirds of PAC and PACG eyes of Chinese patients after LPI had AAC. Plateau iris was accounted for less than 50% of AAC. Other factors such as a thick peripheral iris and an anteriorly inserted iris also contributed to AAC. DRPT results suggested AAC might have more functional meaning than plateau iris.
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Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal.
J. Neurosci.
PUBLISHED: 10-03-2014
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Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression.
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[Chemical constituents of Jasminum giraldii and their antioxidant activity].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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Ten compounds were isolated from the barks of Jasminum giraldii by means of various of chromatographic techniques such as silica gel, Sephadex LH-20 and Rp-HPLC. Their structures were identified by spectroscopic data analysis as (+)-medioresinol (1), (+) -syringaresinol (2), syringaresinol-4'-O-beta-D-glucopyranoside (3), oleanic acid (4), 3-methoxy-4-hydroxy-trans-cinnamaldehyde (5), trans-sinapaldehyde (6), syringaldehyde (7), 1-(4-methoxy -phenyl) -ethanol (8), trans-cinnamic acid (9), and 4-(1-methoxyethyl) -phenol (10). Among them, compounds 1-3, 5-8 and 10 were isolated from the J. genus for the first time and compounds 4 and 9 were obtained from J. giraldii for the first time. In the DPPH free radical scavenging assay, compound 1 exhibited significant activity (IC50 55.1 micromol x L(-1)), compared with vitamin C(IC50 59.9 micromol x L(-1)); and compound 2 showed moderate activity (IC50 79.0 micromol x L(-1)), compared with 2, 6-di-tert-butyl4-methylphenol (IC50 236 micromol x L(-1)).
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Shape-parameterized diffuse optical tomography holds promise for sensitivity enhancement of fluorescence molecular tomography.
Biomed Opt Express
PUBLISHED: 10-01-2014
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A fundamental approach to enhancing the sensitivity of the fluorescence molecular tomography (FMT) is to incorporate diffuse optical tomography (DOT) to modify the light propagation modeling. However, the traditional voxel-based DOT has been involving a severely ill-posed inverse problem and cannot retrieve the optical property distributions with the acceptable quantitative accuracy and spatial resolution. Although, with the aid of an anatomical imaging modality, the structural-prior-based DOT method with either the hard- or soft-prior scheme holds promise for in vivo acquiring the optical background of tissues, the low robustness of the hard-prior scheme to the segmentation error and inferior performance of the soft-prior one in the quantitative accuracy limit its further application. We propose in this paper a shape-parameterized DOT method for not only effectively determining the regional optical properties but potentially achieving reasonable structural amelioration, lending itself to FMT for comparably improved recovery of fluorescence distribution.
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MicroRNA profiles and potential regulatory pattern during the early stage of spermatogenesis in mice.
Sci China Life Sci
PUBLISHED: 09-29-2014
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Spermatogenesis is a complicated and poorly understood process that relies on the precise regulation of the self-renewal and differentiation of spermatogonia. In many organisms, microRNAs (miRNAs) are involved in multiple developmental processes as critical regulators of transcriptional and post-transcriptional gene silencing. This study investigated the expression pattern of miRNAs in type B spermatogonia cells (BSc) and primary spermatocytes (PSc) of mice, using a high-throughput small RNA sequencing system. The results revealed that the expression levels of Let-7 family miRNAs were remarkably high in both cell types. Furthermore, the expression levels of miR-21, miR-140-3p, miR-103, miR-30a, miR-101b and miR-99b were decreased during the transformation from BSc to PSc. These miRNAs target vital genes that participate in apoptosis, cell proliferation and differentiation, junction assembly and cell cycle regulation. These results highlight the indispensable role of miRNAs in spermatogenesis.
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The TRIM-NHL Protein LIN-41 and the OMA RNA-Binding Proteins Antagonistically Control the Prophase-to-Metaphase Transition and Growth of Caenorhabditis elegans Oocytes.
Genetics
PUBLISHED: 09-28-2014
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In many animals, oocytes enter meiosis early in their development but arrest in meiotic prophase I. Oocyte growth, which occurs during this arrest period, enables the acquisition of meiotic competence and the capacity to produce healthy progeny. Meiotic resumption, or meiotic maturation, involves the transition to metaphase I (M phase) and is regulated by intercellular signaling and cyclin-dependent kinase activation. Premature meiotic maturation would be predicted to diminish fertility as the timing of this event, which normally occurs after oocyte growth is complete, is crucial. In the accompanying paper, we identified the highly conserved TRIM-NHL protein LIN-41 as a translational repressor that copurifies with OMA-1 and OMA-2, RNA-binding proteins redundantly required for normal oocyte growth and meiotic maturation. Here we show that LIN-41 enables the production of high-quality oocytes and plays an essential role in controlling and coordinating oocyte growth and meiotic maturation. lin-41 null mutants display a striking defect that is specific to oogenesis: pachytene-stage cells cellularize prematurely and fail to progress to diplotene. Instead, these cells activate CDK-1, enter M phase, assemble spindles, and attempt to segregate chromosomes. Translational derepression of the CDK-1 activator CDC-25.3 appears to contribute to premature M-phase entry in lin-41 mutant oocytes. Genetic and phenotypic analyses indicate that LIN-41 and OMA-1/2 exhibit an antagonistic relationship, and we suggest that translational regulation by these proteins could be important for controlling and coordinating oocyte growth and meiotic maturation. ?
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Mesenchymal Stem Cells Promote Epithelial to Mesenchymal Transition and Metastasis in Gastric Cancer though Paracrine Cues and Close Physical Contact.
J. Cell. Biochem.
PUBLISHED: 09-21-2014
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Mesenchymal stem cells (MSCs) have been shown to integrate into the tumor stroma; however, the precise mechanisms of this process are still elusive. In this study, the EMT phenotype and the enhanced metastatic ability of tumor cells were observed using transwell and trans-endothelial migration assays, respectively, as well as by using electron and laser confocal microscopy. Critical genes were screened and validated using gene arrays and clinical samples, and the changes at the protein level were examined both in vitro and in vivo. Cancer cells acquired an "activated" carcinoma-associated fibroblasts (CAFs) phenotype after being in close contact with MSCs and enhancing tumor metastasis and growth in vivo. Paracrine signals also induced EMT and promoted transwell and trans-endothelial migration, the changes were dependent on ?-catenin, MMP-16, snail and twist. Notably, the higher expression levels of ?-catenin and MMP-16 were correlated with tumor invasion and distant organ and lymph node metastases in intestinal type gastric cancer. MSCs within the tumor niche significantly facilitated tumor growth and metastasis by paracrine cues and close physical connection. This occurred partly through snail, twist and its downstream targets, specifically ?-catenin/MMP-16. This article is protected by copyright. All rights reserved.
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"Out of Pollen" Hypothesis for Origin of New Genes in Flowering Plants: Study from Arabidopsis thaliana.
Genome Biol Evol
PUBLISHED: 09-20-2014
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New genes, which provide material for evolutionary innovation, have been extensively studied for many years in animals where it is observed that they commonly show an expression bias for the testis. Thus, the testis is a major source for the generation of new genes in animals. The source tissue for new genes in plants is unclear. Here, we find that new genes in plants show a bias in expression to mature pollen, and are also enriched in a gene coexpression module that correlates with mature pollen in Arabidopsis thaliana. Transposable elements are significantly enriched in the new genes, and the high activity of transposable elements in the vegetative nucleus, compared with the germ cells, suggests that new genes are most easily generated in the vegetative nucleus in the mature pollen. We propose an "out of pollen" hypothesis for the origin of new genes in flowering plants.
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The Femoral neck Safe Zone: A Radiographic Simulation Study to Prevent Cortical Perforation with Multiple Screw Insertion.
J Orthop Trauma
PUBLISHED: 09-19-2014
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To calculate the probability of iatrogenic perforation when screws appear to be safe on radiographs. A risk zone gradient is mapped to help surgeons determine the suitable screw positions.
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Prevalence and genotype distribution of human papillomavirus among women from Henan, China.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-18-2014
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Human papillomavirus (HPV) infection has been implicated as a causative of cervical cancer. In the present study, a total of 578 samples from females attending the gynecological outpatient clinic in Henan province, China, were collected and the HPV genotypes were detected by gene chip and flow-through hybridization. Overall, 44.5% (257/578) females were found to be HPV DNA positive, and the high risk HPV (HR-HPV) rate was 35.1% (203/578). The first peak of HR-HPV infection appeared in the >60 year-old group (55.0%), and the second was within the 51-55 year-old group (50.0%) (?2=19.497, p<0.05). HPV 16 was the most prevalent genotype (9.2%), followed by HPV 52 (7.8%), HPV 6 (6.9%), HPV 11 (5.9%) and HPV 42 (5.0%). The single type HPV infection was 30.4%, with the five majority prevalent genotype HPV 16 (16.5%), HPV 52 (14.3%), HPV 6 (12.6%), HPV 42 (8.6%), HPV 31 (5.1%). The multiple-type HPV infections were 14.0%, and HPV 16 was the most prevalent type (29.6%), followed by HPV 52 (24.7%), HPV 6 (22.2%), HPV 11 (22.2%), HPV 42 (17.3%) and HPV 39 (17.3%).
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Angiotensin-(1-7) upregulates expression of ABCA1 and ABCG1 through the Mas receptor via the liver X receptor alpha signaling pathway in THP-1 macrophages treated with Angiotensin II.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 09-17-2014
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ATP-binding cassette transporter A1 (ABCA1) and ABCG1 play crucial roles in reverse cholesterol transport and has anti-atherosclerosis effects, and liver X receptor alpha (LXR?) can stimulate cholesterol efflux through these transporters. Angiotensin (Ang)-(1-7) can protect endothelial cells, inhibit smooth muscle cell growth, ameliorate inflammation, and exert anti-atherosclerotic effects. In this study, we attempted to clarify the effect of Ang-(1-7) on expression of ABCA1 and ABCG1, and explored the role of LXR? in the regulation of ABCA1 and ABCG1 in THP-1 macrophages that had been incubated with angiotensin II (AngII). Ang-(1-7) increased ABCA1 and ABCG1 expression in a concentration-dependent manner at both the mRNA and protein levels, promoted cholesterol efflux, and decreased cholesterol content in THP-1 macrophages treated with AngII. Moreover, Ang-(1-7) upregulated the expression of LXR? in a concentration-dependent manner in these cells. LXR? small interfering RNA, as well as the Mas receptor antagonist A-779, completely abolished these effects of Ang-(1-7). In summary, Ang-(1-7) upregulates ABCA1 and ABCG1 expression in THP-1 macrophages treated with AngII through the Mas receptor, via the LXR? pathway. This novel insight into the molecular mechanism underlying Ang-(1-7) and AngII interaction could prove useful for developing new strategies for treatment of cardiovascular diseases. This article is protected by copyright. All rights reserved.
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[The normative combined therapy for recurrent sinusitis].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-16-2014
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To assess the treatment outcome after endoscopic sinus surgery (ESS) in patients with recurrent sinusitis and to research which factors could influence the clinical outcome.
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[Expression of TGF-beta1 and collagen fibers in chronic nasal-sinusitis nasal mucosa of patients].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 09-16-2014
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Explore the TGF-beta1 and collagen fibers in chronic nasal sinusitis each type and degree of expression of the normal control group and in the nasal mucosa epithelial tissue remodeling and the role of TGF-beta1 and collagen deposition relationship.
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[On the necessity of intellectual property rights involving standardization of acupuncture and moxibustion therapies].
Zhen Ci Yan Jiu
PUBLISHED: 09-16-2014
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In the process of working out and implementing standardization of acupuncture-moxibustion (acu-moxi) therapy, the issue of intellectual property rights has been frequently involved. Whether is the standardization inevitably involved in intellectual property rights? A reasonable answer to this question is definitely of important realistic guiding value and significance for acu-moxi standardization work. For this reason, authors of the present paper sum up historical development of correlation between acu-moxi standardization and intellectual property rights, and fully analyze the related causes under the conditions of knowledge economy from 1) increasing protection of acu-moxi intellectual property rights, 2) intrinsic requirements for raising the standardization level of acu-moxi, 3) profits drive of the intellectual property rights owners, and 4) increasing impetuous international economic trade competition.
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Efficient imidation of C(sp3)-H bonds adjacent to oxygen atoms of aryl ethers under metal-free conditions.
Chem. Commun. (Camb.)
PUBLISHED: 09-13-2014
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An intermolecular oxidative C-N formation reaction of aryl ethers with pharmacological saccharins was realized under metal-free conditions for the first time. The understanding of the intrinsic characteristics between C(sp(3))-H and C(sp(2))-O bonds of aryl ethers and their potential for application might promote more research interest in this area.
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[Expression of neural cell adhesion molecule and modification of its N-glycan in ldlD-14 cells].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 09-13-2014
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Neural cell adhesion molecule (NCAM) is a glycoprotein expressing on the surface of neurons, glial cells, bone cells and natural killer cells. NCAM plays an important role in the process of cell - cell adhesion and cell migration, and is also a model protein to study polysialic acid. In this paper, NCAM gene from mouse mammary gland cells (NMuMG) was cloned into eukaryotic expression vectors pcDNA3.1(+) and transfected into mutant Chinese hamster ovary cells ldlD-14. The stable transfection over-expressing NCAM was obtained through the G418 selection and confirmed by Western blotting. Due to unique characters of ldlD-14 cells, carbohydrate chain of NCAM molecule can be easily manipulated with or without adding galactose in the serum free medium, and this modification can provide the basis for further studies on the effect of glycosylation on NCAM molecular function.
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Pak1 Is Required to Maintain Ventricular Ca2+ Homeostasis and Electrophysiological Stability Through SERCA2a Regulation in Mice.
Circ Arrhythm Electrophysiol
PUBLISHED: 09-12-2014
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Impaired sarcoplasmic reticular Ca(2+) uptake resulting from decreased sarcoplasmic reticulum Ca(2+)-ATPase type 2a (SERCA2a) expression or activity is a characteristic of heart failure with its associated ventricular arrhythmias. Recent attempts at gene therapy of these conditions explored strategies enhancing SERCA2a expression and the activity as novel approaches to heart failure management. We here explore the role of Pak1 in maintaining ventricular Ca(2+) homeostasis and electrophysiological stability under both normal physiological and acute and chronic ?-adrenergic stress conditions.
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The effects of China's New Cooperative Medical Scheme on accessibility and affordability of healthcare services: an empirical research in Liaoning Province.
BMC Health Serv Res
PUBLISHED: 09-11-2014
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China's New Cooperative Medical Scheme (NCMS), launched in 2003, was intended to prevent the impoverishment due to catastrophic illness costs. Previous studies have been conducted on the "design flows" of the NCMS, for example, the irrational insurance benefit package. But after several years of implementation, very little has been known about the improvements made by the NCMS and rural residents' attitudes toward it. This article specifically focused on the improvements of healthcare services and the enrollees' choices of providers since the implementation of the NCMS in Liaoning province.
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Regioselective C?H Imidation of Five-Membered Heterocyclic Compounds through a Metal Catalytic or Organocatalytic Approach.
Chem Asian J
PUBLISHED: 09-08-2014
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An efficient method for the synthesis of 2-amino and ?-amino five-membered heterocyclic derivatives that are closely related to a variety of biologically active natural products is described. Regioselectivity was achieved through a metal catalytic or organocatalytic approach. Preliminary studies on the reaction mechanism suggest a radical imidation pathway; however, further studies are needed to verify the mechanism.
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Function and modulation of premotor brainstem parasympathetic cardiac neurons that control heart rate by hypoxia-, sleep-, and sleep-related diseases including obstructive sleep apnea.
Prog. Brain Res.
PUBLISHED: 09-08-2014
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Parasympathetic cardiac vagal neurons (CVNs) in the brainstem dominate the control of heart rate. Previous work has determined that these neurons are inherently silent, and their activity is largely determined by synaptic inputs to CVNs that include four major types of synapses that release glutamate, GABA, glycine, or serotonin. Whereas prior reviews have focused on glutamatergic, GABAergic and glycinergic pathways, and the receptors in CVNs activated by these neurotransmitters, this review focuses on the alterations in CVN activity with hypoxia-, sleep-, and sleep-related cardiovascular diseases including obstructive sleep apnea.
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Horizontal arrangement of anodes of microbial fuel cells enhances remediation of petroleum hydrocarbon-contaminated soil.
Environ Sci Pollut Res Int
PUBLISHED: 09-06-2014
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With the aim of in situ bioremediation of soil contaminated by hydrocarbons, anodes arranged with two different ways (horizontal or vertical) were compared in microbial fuel cells (MFCs). Charge outputs as high as 833 and 762C were achieved in reactors with anodes horizontally arranged (HA) and vertically arranged (VA). Up to 12.5 % of the total petroleum hydrocarbon (TPH) was removed in HA after 135 days, which was 50.6 % higher than that in VA (8.3 %) and 95.3 % higher than that in the disconnected control (6.4 %). Hydrocarbon fingerprint analysis showed that the degradation rates of both alkanes and polycyclic aromatic hydrocarbons (PAHs) in HA were higher than those in VA. Lower mass transport resistance in the HA than that of the VA seems to result in more power and more TPH degradation. Soil pH was increased from 8.26 to 9.12 in HA and from 8.26 to 8.64 in VA, whereas the conductivity was decreased from 1.99 to 1.54 mS/cm in HA and from 1.99 to 1.46 mS/cm in VA accompanied with the removal of TPH. Considering both enhanced biodegradation of hydrocarbon and generation of charge in HA, the MFC with anodes horizontally arranged is a promising configuration for future applications.
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Bone marrow transplantation concurrently reconstitutes donor liver and immune system across host species barrier in mice.
PLoS ONE
PUBLISHED: 09-05-2014
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Liver immunopathologic mechanisms during hepatotropic infection, malignant transformation, and autoimmunity are still unclear. Establishing a chimeric mouse with a reconstituted liver and immune system derived from a single donor across species is critical to study regional donor immune responses in recipient liver. Using a strain of mice deficient in tyrosine catabolic enzyme fumarylacetoacetate hydrolase (fah-/-) and bone marrow transplantation (BMT), we reconstituted the donor's hepatocytes and immune cells across host species barrier. Syngeneic, allogeneic or even xenogeneic rat BMT rescued most recipient fah-/- mice against liver failure by donor BM-derived FAH+ hepatocytes. Importantly, immune system developed normally in chimeras, and the immune cells together with organ architecture were intact and functional. Thus, donor BM can across host species barrier and concurrently reconstitutes MHC-identical response between immune cells and hepatocytes, giving rise to a new simple and convenient small animal model to study donor's liver immune response in mice.
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Energetic requirements of iridium(III) complex based photosensitisers in photocatalytic hydrogen generation.
Phys Chem Chem Phys
PUBLISHED: 09-05-2014
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A new family of Ir(III) complexes were synthesised and employed as light-induced hydrogen-production photosensitisers in aqueous systems, where hydrogen evolution was observed only when the PS* was reduced by the sacrificial agent, NEt3, signifying that a minimum potential difference of >0.2 V between E(PS*/PS(-)) and E(NEt3(+)/NEt3) is required for efficient hydrogen production [i.e., E(PS*/PS(-)) >1.19 V versus NHE]. The analytical method developed here is demonstrated to be useful for screening new photosensitisers for light-driven hydrogen generation.
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Presence of qnr, aac(6')-Ib, qepA, oqxAB, and mutations in gyrase and topoisomerase in nalidixic acid-resistant Salmonella isolates recovered from retail chicken carcasses.
Foodborne Pathog. Dis.
PUBLISHED: 09-05-2014
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Four hundred sixty-two nalidixic acid- and/or ciprofloxacin-resistant Salmonella isolates were examined for presence of quinolone-resistance mechanisms. A total of 339 amino acid substitutions were identified in GyrA (204) and ParC (135). Ser83Phe/Asp87Gly (29.4%) were most commonly detected in GyrA in 136 isolates, and to a lesser extent of Asp87Asn (22.8%), Asp87Gly (19.1%), Ser83Phe/Asp87Asn (19.1%), and Ser83Tyr (5.1%). Ser80Arg (97.0%) was detected in ParC in 132 isolates. Simultaneous mutations in GyrA and ParC (n=109) were commonly detected to be Ser83Phe/Asp87Gly(GyrA)-Ser80Arg(ParC) (35.8%), Asp87Asn(GyrA)-Ser80Arg(ParC) (22.9%), and Ser83Phe/Asp87Asn(GyrA)-Ser80Arg(ParC) (21.1%). qnrA, qnrB, qnrS, aac(6')-Ib, qepA, and oqxAB were detected in 52 (11.3%), 64 (13.9%), 11(2.4%), 107 (23.2%), 6 (1.3%), and 194 (42.0%) of 462 isolates, respectively. Isolates carried more qnr, aac(6')-Ib, qepA, and oqxAB genes, and amino acid substitution in GyrA and ParC was more resistant to nalidixic acid and fluoroquinolones.
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Relationship Between Alcohol Consumption and Serum Lipid Profiles Among Middle-Aged Population in China: A Multiple-Center Cardiovascular Epidemiological Study.
Angiology
PUBLISHED: 09-04-2014
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We assessed the relationship between alcohol consumption and serum lipids in a middle-aged Chinese population. The overall prevalence of drinking among 10 154 participants was 34.07% in males and 3.61% in females. Heavy alcohol drinkers (? 30 g/d) tended to be older, smokers, hypertensive, do heavy physical activity, and have a lower body mass index. Levels of high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) A1, low-density lipoprotein cholesterol-HDL-C ratio, and apo B-apo A1 ratio rose with increase in alcohol intake in males. An increase of 0.27 mmol/L in triglycerides and a decrease of 2.10 mg/dL in lipoprotein(a), Lp(a), were observed in male alcohol drinkers who consumed ?30 g alcohol/d compared with abstainers after controlling for all confounders. Levels of total cholesterol, HDL-C, and apo A1 increased with increase in alcohol intake in both genders and Lp(a) decreased with the increase in alcohol intake in males.
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The secreted peptide PIP1 amplifies immunity through receptor-like kinase 7.
PLoS Pathog.
PUBLISHED: 09-04-2014
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In plants, innate immune responses are initiated by plasma membrane-located pattern recognition receptors (PRRs) upon recognition of elicitors, including exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Arabidopsis thaliana produces more than 1000 secreted peptide candidates, but it has yet to be established whether any of these act as elicitors. Here we identified an A. thaliana gene family encoding precursors of PAMP-induced secreted peptides (prePIPs) through an in-silico approach. The expression of some members of the family, including prePIP1 and prePIP2, is induced by a variety of pathogens and elicitors. Subcellular localization and proteolytic processing analyses demonstrated that the prePIP1 product is secreted into extracellular spaces where it is cleaved at the C-terminus. Overexpression of prePIP1 and prePIP2, or exogenous application of PIP1 and PIP2 synthetic peptides corresponding to the C-terminal conserved regions in prePIP1 and prePIP2, enhanced immune responses and pathogen resistance in A. thaliana. Genetic and biochemical analyses suggested that the receptor-like kinase 7 (RLK7) functions as a receptor of PIP1. Once perceived by RLK7, PIP1 initiates overlapping and distinct immune signaling responses together with the DAMP PEP1. PIP1 and PEP1 cooperate in amplifying the immune responses triggered by the PAMP flagellin. Collectively, these studies provide significant insights into immune modulation by Arabidopsis endogenous secreted peptides.
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Discovery of potent N-(isoxazol-5-yl)amides as HSP90 inhibitors.
Eur J Med Chem
PUBLISHED: 08-26-2014
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HSP90 is ubiquitously overexpressed in a broad spectrum of human cancers and has been recognized as an attractive target for cancer treatment. Here, we described the fragment screening, synthesis and structure-activity relationship studies of small molecule inhibitors with 4,5-diarylisoxazole scaffold targeting HSP90. Among them, the compound N-(3-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-((4-morpholinopiperidin-1-yl)methyl)phenyl)isoxazol-5-yl)cyclopropanecarboxamide (108) showed high affinity for binding to HSP90 (FP binding assay, IC50 = 0.030 ?M) and inhibited the proliferation of various human cancer cell lines with averaging GI50 about 88 nM. Compound 108 exhibited its functional inhibition of HSP90 by depleting key signaling pathways and concomitantly elevating of HSP70 and HSP27 in U-87MG cells. Further in vivo studies showed that compound 108 strongly suppressed the tumor growth of human glioblastoma xenograft model U-87MG with T/C = 18.35% at 50 mg/kg q3w/2.5w. Moreover, compound 108 also exhibited good pharmacokinetic properties. Together, our study implicates that compound 108 is a promising candidate of HSP90 inhibitor and is currently advanced to preclinical study.
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Effects of Cucurbitacin E, a Tetracyclic Triterpene Compound from Cucurbitaceae, on the Pharmacokinetics and Pharmacodynamics of Warfarin in Rats.
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 08-17-2014
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This study firstly investigated the effects of cucurbitacin E (CuE), a tetracyclic triterpene compound from Cucurbitaceae, on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin, a model CYP2C probe substrate, in the rat. In PK studies, the concentration of warfarin in blood samples was determined by HPLC-DAD, and the PK parameters were analysed using non-compartmental methods. In PD studies, the prothrombin time (PT) in blood plasma at each sample point was measured via thromboplastin reagents. CuE treatment (50, 100 and 200 ?g/kg, i.p.) decreased warfarin clearance (28-32%), increased the area under the curve (AUC0-? ; 55-62%) and prolonged plasma half-life (t1/2 ; 58-72%). At the same time, the anticoagulation effect of warfarin (PTmax ) was also significantly increased in the presence of CuE. These data demonstrated that CuE affected the PK and PD of warfarin, and these effects may be due to the inhibition of CYP2C activity by CuE. Hence, careful monitoring should be carried out during concomitant use of herbal products containing CuE with drugs that are metabolized by CYP2C enzymes.
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Differential diagnosis of eccrine spiradenoma: A case report.
Exp Ther Med
PUBLISHED: 08-14-2014
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Eccrine spiradenoma (ES) is a rare, benign adnexal neoplasm that may easily be mistaken for glomus lesions or angioleiomyoma due to its painfulness and florid vascularization. A 44-year-old male with a blue-colored, nodular tumor on the left knee, present for 10 years, was submitted for diagnosis. Dermatological examination was undertaken, followed by surgical excision of the subcutaneous lesion and histopathological examination of the tissue. Subjective symptoms included tenderness upon palpation and routine investigations were within normal limits. Immunohistochemical analysis of the tumor cells demonstrated positive staining for CK5/CK6, CK8/CK18, S100, as well as small vacuole-like positive for EMA, and was therefore diagnosed as ES. The results of the present study suggest that immunohistochemical assays may be helpful to clarify the diagnosis and differentiate ES from other painful subcutaneous tumors exhibiting similar clinical and histological presentations.
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Effects of ACEI/ARB in hypertensive patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled studies.
BMC Cardiovasc Disord
PUBLISHED: 08-08-2014
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The effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on cardiovascular (CV) risk in hypertensive patients with type 2 diabetes mellitus (T2 DM) are uncertain. Our objective was to analyze the effects of ACE/ARBs, on the incidence of myocardial infarction, stroke, CV events, and all-cause mortality in hypertensive patients with T2 DM.
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OsAUX1 controls lateral root initiation in rice (Oryza sativa L.).
Plant Cell Environ.
PUBLISHED: 08-07-2014
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Polar auxin transport, mediated by influx and efflux transporters, controls many aspects of plant growth and development. The auxin influx carriers in Arabidopsis have been shown to control lateral root development and gravitropism, but little is known about these proteins in rice. This paper reports on the functional characterization of OsAUX1. Three OsAUX1 T-DNA insertion mutants and RNAi knockdown transgenic plants reduced lateral root initiation compared to WT plants. OsAUX1 overexpression plants exhibited increased lateral root initiation and OsAUX1 was highly expressed in lateral roots and lateral root primordia. Similarly, the auxin reporter, DR5-GUS, was expressed at lower levels in osaux1 than in the WT plants, which indicated that the auxin levels in the mutant roots had decreased. Exogenous NAA treatment rescued the defective phenotype in osaux1-1 plants, whereas IAA and 2,4-D could not, which suggested that OsAUX1 was a putative auxin influx carrier. The transcript levels of several auxin-signaling genes and cell cycle genes significantly declined in osaux1, hinting that the regulatory role of OsAUX1 may be mediated by auxin-signaling and cell cycle genes. Overall, our results indicated that OsAUX1 was involved in polar auxin transport and functioned to control auxin-mediated lateral root initiation in rice.
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Waltonitone induces apoptosis through mir-663-induced Bcl-2 downregulation in non-small cell lung cancer.
Tumour Biol.
PUBLISHED: 07-24-2014
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Our previous study reported that waltonitone treatment inhibited proliferation and induced apoptosis of lung cancer cells. However, the mechanism of waltonitone-induced toxicity remains unclear. In the present study, we treated H460 and H3255 lung cancer cells using different concentration of waltonitone (0, 10, 20, 30 ?mol/L). We observed that waltonitone inhibited cell viability and induced apoptosis in a concentration dependent manner, with upregulation of caspase-3 cleavage. We also observed upregulation of miR-663, a potential tumor suppressor, after waltonitone treatment. Suppression of miR-663 function using miR-663 inhibitor partly alleviated cell toxicity induced by waltonitone. In addition, both waltonitone treatment and transfection of miR-663 mimic upregulated Bcl-2 mRNA and protein expression. Bcl-2 transfection alleviated waltonitone-induced toxicity. Furthermore, transfection of miR-663 inhibitor upregulated Bcl-2 levels in both cell lines. In summary, the present study demonstrated that waltonitone induced apoptosis of lung cancer cells through, at least partly, miR-663-induced Bcl-2 downregulation.
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Paradoxical role of CBX8 in proliferation and metastasis of colorectal cancer.
Oncotarget
PUBLISHED: 07-23-2014
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The effect of polycomb chromobox (Cbx) proteins in cancer is context-dependent. The Chromobox homolog 8 (CBX8) was originally characterized as a transcriptional repressor, which inhibits cell proliferation in Ink4a-Arf-dependent and -independent manner. However, the role of CBX8 in colorectal cancer remains unknown. Here, we found that high CBX8 expression was associated with a low rate of distant metastasis and good prognosis in CRC patients, even though CBX8 was up-regulated in CRC cell lines and clinical samples. Knockdown of CBX8 inhibited CRC proliferation in vitro and in vivo, mostly by increasing p53 and its downstream effectors. However, knockdown of CBX8 enhanced CRC migration, invasion and metastasis in vitro and in vivo, in part through direct up-regulation of integrin ?4 (ITGB4) that in turn decreased RhoA activity. Collectively, the knockdown of CBX8 inhibited CRC proliferation, while promoting its metastasis, thus exerting paradoxical effects in CRC progression.
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Temperature sensing in seawater based on microfiber knot resonator.
Sensors (Basel)
PUBLISHED: 07-21-2014
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Ocean internal-wave phenomena occur with the variation in seawater vertical temperature, and most internal-wave detections are dependent on the measurement of seawater vertical temperature. A seawater temperature sensor based on a microfiber knot resonator (MKR) is designed theoretically and demonstrated experimentally in this paper. Especially, the dependences of sensing sensitivity on fiber diameter and probing wavelength are studied. Calculated results show that sensing sensitivity increases with the increasing microfiber diameter with the range of 2.30-3.91 ?m and increases with the increasing probing wavelength, which reach good agreement with results obtained by experiments. By choosing the appropriate parameters, the maximum sensitivity measured can reach to be 22.81 pm/°C. The seawater temperature sensor demonstrated here shows advantages of small size, high sensitivity, easy fabrication, and easy integration with fiber systems, which may offer a new optical method to detect temperature of seawater or ocean internal-wave phenomenon and offer valuable reference for assembling micro sensors used for other parameters related to seawater, such as salinity, refractive index, concentration of NO3- and so on.
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Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung cancer cells.
Mol Med Rep
PUBLISHED: 07-21-2014
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Natural products are a great source of cancer chemotherapeutic agents. The present study was conducted to investigate whether cucurbitacin B (CuB), one of the most potent and widely used cucurbitacins, inhibits proliferation and induces apoptosis in the A549 lung cancer cell line. Furthermore, CuB induced apoptosis of A549 cells in a -concentration-dependent manner, as determined by fluorescence microscopy, flow cytometry and transmission electron microscopy. The present study also demonstrated that CuB dose-dependently inhibited lung cancer cell proliferation, with cell cycle inhibition and cyclin B1 downregulation. Apoptosis induced by CuB was shown to be associated with cytochrome c release, B-cell lymphoma 2 downregulation and signal transducer and activator of transcription 3 pathway inhibition. CuB may prove to be a useful approach for the chemotherapy of lung cancer.
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Effect of hydraulic retention time (HRT) on the biodegradation of trichloroethylene wastewater and anaerobic bacterial community in the UASB reactor.
Appl. Microbiol. Biotechnol.
PUBLISHED: 07-19-2014
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This study utilizes the unique merits of an 8-L laboratory upflow anaerobic sludge blanket (UASB) reactor for treating synthetic wastewater containing trichloroethylene (TCE). The reactor was operated at different hydraulic retention times (HRT) of 25, 20, 15, 10, and 5 h. TCE removal efficiency decreased from 99 to 85 % when the HRT was lowered down from 25 to 5 h, as well as chemical oxygen demand (COD) removal efficiency (from 95 to 84.15 %). Using Illumina 16S rRNA gene MiSeq sequencing, we investigated the evolution of bacterial communities in the anaerobic sludge under five different conditions of HRT. In total, 106,387 effective sequences of the 16S rRNA gene were generated from 5 samples that widely represented the diversity of microbial community. Sequence analysis consisting of several novel taxonomic levels ranging from phyla to genera revealed the percentages of these bacterial groups in each sample under different HRTs. The differences found among the five samples indicated that HRT had effects on the structures of bacterial communities and the changes of bacterial communities associated with the effect of HRT on the performance of the reactor. Sequence analyses showed that Bacteroidetes and Firmicutes were the dominant phyla. It is notable that the class Dehalococcoidia was found in the samples at HRT of 5, 10, 20, and 25 h, respectively, in which there were some dechlorination strains. Moreover, a tremendous rise of TCE removal efficiency from HRT of 5 h to HRT of 10 h was found.
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Arsenite promotes intestinal tumor cell proliferation and invasion by stimulating epithelial-to-mesenchymal transition.
Cancer Biol. Ther.
PUBLISHED: 07-10-2014
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Arsenite (AS) is a ubiquitous environmental element that is widely present in food, soil, and water. Environmental exposure to AS represents a major global health concern, because AS is a well-established human carcinogen. We hypothesize that low concentration of AS could enhance metastasis and proliferation of transformed cancer cells by promoting EMT. To test this hypothesis, we treated human colorectal cancer cells with low concentration of AS, and then measured the multiple readouts of cell viability, proliferation, migration, and adhesion in vitro and in vivo. Collectively, our data indeed strongly support our hypothesis and shed novel light into this important pathophysiological process. These novel insights are not only of high interests to basic cancer research, but may also have direct implications in cancer prevention and treatment.
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Somatic mutations of the HER2 in metastatic breast cancer.
Tumour Biol.
PUBLISHED: 07-06-2014
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Mutations in the epidermal growth factor receptor gene (EGFR) in lung cancers predict for sensitivity to EGFR kinase inhibitors. HER2 (also known as NEU, EGFR2, or ERBB2) is a member of the EGFR family of receptor tyrosine kinases and plays important roles in the pathogenesis of certain human cancers, and mutations have recently been reported in lung cancers. We sequenced the full length of HER2 in 198 metastatic breast cancers (MBC) as well as 34 other epithelial cancers (bladder, prostate, and colorectal cancers) and compared the mutational status with clinic pathologic features and the presence of EGFR or KRAS mutations. HER2 mutations were present in 11.6 % (23 of 198) of MBC and were absent in other types of cancers. HER2 mutations were located in exon 15 and the in-frame insertions in exon 20 with corresponding region as did EGFR insertions. HER2 mutations were significantly more frequent in patient after the administration of trastuzumab (34.8 %, 8 of 23; P?=?0.02). Mutations in exon 15 and 20 were more potent than wild-type HER2 in associating with activating signal transducers and inducing survival, invasiveness, and tumorigenicity.
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The Impact of Tumor Cell Differentiation on Survival of Patients with Resectable Esophageal Squamous Cell Carcinomas.
Ann. Surg. Oncol.
PUBLISHED: 07-05-2014
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The current American Joint Committee on Cancer staging system considers tumor cell differentiation grade to be a factor in the staging of esophageal squamous cell carcinoma (ESCC) in pathologic T0-3N0M0 cases. However, more data are essential to test its efficacy. We sought to investigate the tumor-node-metastasis categories for which tumor cell grade might affect overall survival in Chinese patients.
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Record antiferromagnetic coupling for a 3d/4d cyanide-bridged compound.
J. Am. Chem. Soc.
PUBLISHED: 06-30-2014
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The pentanuclear compound [V(II)(tmphen)2]3[Mo(III)(CN)6]2 (tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline) exhibits a record antiferromagnetic exchange coupling constant of J(V-Mo) = -114 cm(-1). This is the first example of a heterobimetallic cyanide compound with such strong magnetic coupling.
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Combination of Apolipoprotein A1-Modi Liposome-Doxorubicin with Autophagy Inhibitors Overcame Drug Resistance In Vitro.
J Pharm Sci
PUBLISHED: 06-27-2014
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Multidrug resistance (MDR) represents the major drawback in chemotherapy. Liposome-based approaches could reverse MDR to some extent through circumventing the active efflux effect of P-glycoprotein. However, the reverse power of liposome is very limited because the nontargeting liposome is inefficient to deliver drugs to tumor actively. Besides, autophagy could reinforce the resistance of tumor cells to the cytotoxicity of intracellular drugs. Here, liposomal doxorubicin (Lipodox) that was conjugated with apolipoprotein A1-apo-Lipodox, was employed in tumor targeting delivery of doxorubicin. In the experiments, apo-Lipodox could enter cells effectively and reverse MDR more efficiently than their nontargeting counterpart. Autophagy occurred in this process and contributed to the survival of tumor cells. Combination use of autophagy inhibitors could enhance the cytotoxicity of apo-Lipodox and reverse drug resistance to a higher degree. We propose that this strategy holds promise to overcome MDR in human cancer. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3994-4004, 2014.
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Mycobacterium tuberculosis Erdman infection of rhesus macaques of Chinese origin.
Tuberculosis (Edinb)
PUBLISHED: 06-27-2014
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Continuous high global tuberculosis (TB) mortality rates and variable vaccine efficacy of mycobacterium Bacille Calmette-Guérin (BCG) emphasize the need for improved vaccines and drugs against TB, which require clinically relevant animal models for evaluation. We infected a total of 24 Chinese rhesus macaques with varying doses (CFU of 25, 100 and 500) of Mycobacterium tuberculosis (M.tb) Erdman strain via bronchoscopy. Regardless of the M.tb doses, all animals were infected successfully with minor differences in clinical progression; as evidenced by clinical manifestations, laboratory analyses, bacterial burden in infected tissues and histopathology evaluations. Rhesus macaques of Chinese origin are highly susceptible to infection with M.tb Erdman strain and develop acute TB disease, which is similar to that in humans. Pathologically, Chinese rhesus macaques recapitulated the complete spectrum of granulomatous lesions seen in human TB disease. These data indicate that low-dose infection of rhesus macaques of Chinese origin is a suitable model for acute M.tb infection.
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One-Pot Glovebox-Free Synthesis, Characterization, and Self-Assembly of Novel Amphiphilic Poly(Sarcosine-b-Caprolactone) Diblock Copolymers.
Macromol Rapid Commun
PUBLISHED: 06-19-2014
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Novel amphiphilic polypeptoid-polyester diblock copolymers based on poly(sarcosine) (PSar) and poly(?-caprolactone) (PCL) are synthesized by a one-pot glovebox-free approach. In this method, sarcosine N-carboxy anhydride (Sar-NCA) is firstly polymerized in the presence of benzylamine under N2 flow, then the resulting poly(sarcosine) is used in situ as the macro-initiator for the ring-opening polymerization (ROP) of ?-caprolactone using tin(II) octanoate as a catalyst. The degree of poly-merization of each block is controlled by various feed ratios of monomer/initiator. The diblock copolymers with controlled molecular weight and narrow molecular weight distributions (?M < 1.2) are characterized by (1) H NMR, (13) C NMR, and size-exclusion chromatography. The self-assembly behavior of PSar-b-PCL in water is investigated by dynamic light scattering (DLS) and transmission electron microscopy. DLS results reveal that the diblock copolymers associate into nanoparticles with average hydrodynamic diameters (DH ) around 100 nm in water, which may be used as drug delivery carriers.
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Vector competence of the tick Ixodes sinensis (Acari: Ixodidae) for Rickettsia monacensis.
Parasit Vectors
PUBLISHED: 06-11-2014
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BackgroundCases of Mediterranean Spotted Fever like rickettsioses, caused by Rickettsia monacensis, have become more common in the last 10 years. In China, natural infection of R. monacensis in various tick species has been confirmed but the vector(s) of R. monacensis have not been recorded.MethodsThe prevalence of R. monacensis in >1500 Ixodidae ticks from central and southern China was determined using centrifugation-shell vial culture and polymerase chain reaction techniques. The predominant species, Ixodes sinensis, harbored a natural infection of R. monacensis and was assumed to be a vector candidate of R. monacensis. Experimental transmissions were initialized by infecting Rickettsia-free tick colonies with R. monacensis using capillary tube feeding (CTF) or immersion techniques. Transstadial and transovarial transmissions, and transmission from ticks to mice, were conducted under laboratory conditions.Results R. monacensis was isolated and identified from hemolymph of Ixodes sinensis using molecular techniques. Transovarial transmission of R. monacensis from infected ¿I. sinensis to offspring was documented and infected offspring successfully passed Rickettsia to mice. Transstadial transmission rates were 58% in larva to nymph and 56% in nymph to adult stages. Infected nymphs and adults were also able to infect mice.Conclusions I. sinensis is a competence vector for R. monacensis as demonstrated by natural infection and transmission studies.
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Cell-based therapy for acute and chronic liver failures: distinct diseases, different choices.
Sci Rep
PUBLISHED: 06-10-2014
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Cell-based therapies (CBTs) are considered the effective approaches to treat liver failure. However, which cell type is the most suitable source of CBTs for acute liver failure (ALF) or chronic liver failure (CLF) remains unclear. To investigate this, mature hepatocytes in adult liver (adult HCs), fetal liver cells (FLCs), induced hepatic stem cells (iHepSCs) and bone marrow derived mesenchymal stromal cells (BMSCs) were used to CBTs for ConA-induced ALF and Fah-deficient induced CLF in mice. The results showed that only BMSCs remitted liver damage and rescued ALF in ConA-treated mice. In this process, BMSCs inhibited ConA-induced inflammatory response by decreasing the mRNA expressions of TNF-?, IFN-? and FasL and increasing IL-10 mRNA expression. However, in the CLF model, not BMSCs but adult HCs transplantation lessened liver injury, recovered liver function and rescued the life of Fah-/- mice after NTBC withdrawal. Further study showed that adult HCs offered more effective liver regeneration compared to other cells in Fah-/- mice without NTBC. These results demonstrated that BMSCs and adult HCs are the optimal sources of CBTs for ConA-induced ALF and Fah-deficient induced CLF in mice, respectively. This finding deepens our understanding about how to select a proper CBT for different liver failure.
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Neuroprotective agents target molecular mechanisms of disease in ALS.
Drug Discov. Today
PUBLISHED: 06-09-2014
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Amyotrophic lateral sclerosis (ALS) is a debilitating disease characterized by progressive loss of voluntary motor neurons leading to muscle atrophy, weight loss and respiratory failure. Evidence suggests that inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and proteasomal dysfunction are all responsible for ALS pathogenesis. We review neuroprotective agents with the ability to reduce ALS-related bodyweight loss, summarize the various therapies tested on animal models targeting the proposed molecular mechanisms, compare their effects on bodyweight loss, muscle damage, disease onset, duration and survival, and analyze their structure-activity relationships, with the overall goal of creating a screening strategy for further clinical application.
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Identification of important residues of insulin-like peptide 5 and its receptor RXFP4 for ligand-receptor interactions.
Arch. Biochem. Biophys.
PUBLISHED: 06-08-2014
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Insulin-like peptide 5 (INSL5) is an insulin/relaxin superfamily peptide involved in the regulation of glucose homeostasis by activating its receptor RXFP4, which can also be activated by relaxin-3 in vitro. To determine the interaction mechanism of INSL5 with its receptor RXFP4, we studied their electrostatic interactions using a charge-exchange mutagenesis approach. First, we identified three negatively charged extracellular residues (Glu100, Asp104 and Glu182) in human RXFP4 that were important for receptor activation by wild-type INSL5. Second, we demonstrated that two positively charged B-chain Arg residues (B13Arg and B23Arg) in human INSL5 were involved in receptor binding and activation. Third, we proposed probable electrostatic interactions between INSL5 and RXFP4: the B-chain central B13Arg of INSL5 interacts with both Asp104 and Glu182 of RXFP4, meanwhile the B-chain C-terminal B23Arg of INSL5 interacts with both Glu100 and Asp104 of RXFP4. The present electrostatic interactions between INSL5 and RXFP4 were similar to our previously identified interactions between relaxin-3 and RXFP4, but had subtle differences that might be caused by the different B-chain C-terminal conformations of relaxin-3 and INSL5 because a dipeptide exchange at the B-chain C-terminus significantly decreased the activity of INSL5 and relaxin-3 to receptor RXFP4.
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