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Find video protocols related to scientific articles indexed in Pubmed.
PICK1 Mediates Synaptic Recruitment of AMPA Receptors at Neurexin-Induced Postsynaptic Sites.
J. Neurosci.
PUBLISHED: 11-14-2014
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In the CNS, synapse formation and maturation play crucial roles in the construction and consolidation of neuronal circuits. Neurexin and neuroligin localize on the opposite sides of synaptic membrane and interact with each other to promote the assembly and specialization of synapses. However, the excitatory synapses induced by the neurexin-neuroligin complex are initially immature synapses that lack AMPA receptors. Previously, PICK1 (protein interacting with C kinase 1) was shown to cluster and regulate the synaptic localization of AMPA receptors. Here, we report that during synaptogenesis induced by neurexin in cultured neurons from rat hippocampus, PICK1 recruited AMPA receptors to immature postsynaptic sites. This synaptic recruitment of AMPA receptors depended on the interaction between GluA2 and PICK1, and on the lipid-binding ability of PICK1, but not the interaction between PICK1 and neuroligin. Last, our results demonstrated that the recruitment of GluA2 to synapses could be prevented by ICA69 (islet cell autoantigen 69 kDa), a key binding partner of PICK1. Our study showed that PICK1, being negatively regulated by ICA69, could facilitate synapse maturation.
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Common Variants in the MKL1 Gene Confer Risk of Schizophrenia.
Schizophr Bull
PUBLISHED: 11-09-2014
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Genome-wide association studies (GWAS) of schizophrenia have identified multiple risk variants with robust association signals for schizophrenia. However, these variants could explain only a small proportion of schizophrenia heritability. Furthermore, the effect size of these risk variants is relatively small (eg, most of them had an OR less than 1.2), suggesting that additional risk variants may be detected when increasing sample size in analysis. Here, we report the identification of a genome-wide significant schizophrenia risk locus at 22q13.1 by combining 2 large-scale schizophrenia cohort studies. Our meta-analysis revealed that 7 single nucleotide polymorphism (SNPs) on chromosome 22q13.1 reached the genome-wide significance level (P < 5.0×10(-8)) in the combined samples (a total of 38441 individuals). Among them, SNP rs6001946 had the most significant association with schizophrenia (P = 2.04×10(-8)). Interestingly, all 7 SNPs are in high linkage disequilibrium and located in the MKL1 gene. Expression analysis showed that MKL1 is highly expressed in human and mouse brains. We further investigated functional links between MKL1 and proteins encoded by other schizophrenia susceptibility genes in the whole human protein interaction network. We found that MKL1 physically interacts with GSK3B, a protein encoded by a well-characterized schizophrenia susceptibility gene. Collectively, our results revealed that genetic variants in MKL1 might confer risk to schizophrenia. Further investigation of the roles of MKL1 in the pathogenesis of schizophrenia is warranted.
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Delitschiapyrone A, a Pyrone-Naphthalenone Adduct Bearing a New Pentacyclic Ring System from the Leaf-Associated Fungus Delitschia sp. FL1581.
Org. Lett.
PUBLISHED: 11-03-2014
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Delitschiapyrone A (1), an ?-pyrone-naphthalenone adduct with an unprecedented pentacyclic ring system, was isolated from a solid culture of the leaf-associated fungus Delitschia sp. FL1581. The structure of 1 was elucidated by spectroscopic analysis and X-ray crystallography, and its absolute configuration was defined by experimental and calculated ECD. Biosynthetically, the unique 6/6/5/7/6 pentacyclic core of 1 may be formed by an intermolecular Diels-Alder-type addition of the precursors derived from (1'R)-2',3'-dihydropyrenocine C (2) and 6-ethyl-2,7-dimethoxyjuglone (3) found to co-occur with 1 in this fungus.
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[Exploration and practice of research-based teaching in the course of theory of Meridians and Acupoints for acupuncture and tuina specialty].
Zhongguo Zhen Jiu
PUBLISHED: 10-23-2014
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For the purpose of exploring the teaching reform model and method, also promoting the quality of talents in acupuncture and tuina field, the research-based teaching model is applied into the course of Theory of Meridians and Acupoints. This method includes two parts of teaching and learning. For teachers, they bring modern research focus and trend into teaching through questionnaire survey among students, aiming to integrate the education inside and outside class. For students, they are guided to resolve the opening, enlightening and scalable issues through consulting abundant resources of literature and database to achieve autonomous participation in the course of learning. By this teaching method, it is expected to train the student's ability of expanding their thinking, as well as discovering, analyzing and solving the problem.
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The complete mitochondrial genome of Cheilinus undulates based on high-throughput sequencing technique.
Mitochondrial DNA
PUBLISHED: 10-21-2014
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Abstract Cheilinus undulatus is a Critically Endangered ocean fish, which is also a higher level predator in coral reef. The complete mitochondrial genome of Cheilinus undulatus has been sequenced by high-throughput sequencing technology. According to the results, the mitochondrial genome of Cheilinus undulatus is 17,184?bp long and consists of 38 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region. The nucleotides compositions of the light strand are 27.62% of A, 24.82% of T, 16.66% of G and 30.90% of C. With the exception of ND6 and 8 tRNA genes, all other mitochondrial genes are encoded on the heavy strand. C. undulates mitochondrial genome contains a 568?bp sequences that is a non-coding DNA domain. No homology sequence had been found through BLAST in GenBank. The sequences are probably characteristic species marker of C. undulates.
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Cytotoxic Resin Glycosides from Ipomoea aquatica and Their Effects on Intracellular Ca(2+) Concentrations.
J. Nat. Prod.
PUBLISHED: 10-14-2014
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Eleven new resin glycosides, aquaterins I-XI (1-11), were isolated from the whole plants of Ipomoea aquatica. The structures of 1-11 were elucidated by a combination of spectroscopic and chemical methods. They were found to be partially acylated tetra- or pentasaccharides derived from simonic acid B and operculinic acids A and C. The site of the aglycone macrolactonization was placed at C-2 or C-3 of the second saccharide moiety, while the two acylating residues could be located at C-2 (or C-3) of the second rhamnose unit and at C-4 (or C-3) on the third rhamnose moiety. All compounds were evaluated for cytotoxicity against a small panel of human cancer cell lines. Compound 4 exhibited the most potent activity against HepG2 cells with an IC50 value of 2.4 ?M. Cell cycle analysis revealed 4 to inhibit the proliferation of HepG2 cells via G0/G1 arrest and apoptosis induction. In addition, compounds 1-4, 7, 9, and 10 were found to elevate Ca(2+) in HepG2 cells, which might be involved in the regulation of the cytotoxic activities observed.
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GPR126 Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Signaling.
J. Biol. Chem.
PUBLISHED: 09-14-2014
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Angiogenesis, the formation of new blood vessels from preexisting ones, is essential for development, wound healing, and tumor progression. The VEGF pathway plays irreplaceable roles during angiogenesis, but how other signals crosstalk with and modulate VEGF cascades is not clearly elucidated. Here, we identified that Gpr126, an endothelial cell enriched gene, plays an important role in angiogenesis by regulating endothelial cell proliferation, migration, and tube formation. Knockdown of Gpr126 in the mouse retina resulted in the inhibition of hypoxia-induced angiogenesis. Interference of Gpr126 expression in zebrafish embryos led to defects in intersegmental vessel formation. Finally, we identified that GPR126 regulated the expression of VEGFR2 by targeting STAT5 and GATA2 through the cAMP-PKA-CREB signaling pathway during angiogenesis. Our findings illustrate that GPR126 modulates both physiological and pathological angiogenesis through VEGF signaling, providing a potential target for the treatment of angiogenesis-related diseases.
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A nontumorigenic variant of FGF19 treats cholestatic liver diseases.
Sci Transl Med
PUBLISHED: 08-01-2014
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Hepatic accumulation of bile acids is central to the pathogenesis of cholestatic liver diseases. Endocrine hormone fibroblast growth factor 19 (FGF19) may reduce hepatic bile acid levels through modulation of bile acid synthesis and prevent subsequent liver damage. However, FGF19 has also been implicated in hepatocellular carcinogenesis, and consequently, the potential risk from prolonged exposure to supraphysiological levels of the hormone represents a major hurdle for developing an FGF19-based therapy. We describe a nontumorigenic FGF19 variant, M70, which regulates bile acid metabolism and, through inhibition of bile acid synthesis and reduction of excess hepatic bile acid accumulation, protects mice from liver injury induced by either extrahepatic or intrahepatic cholestasis. Administration of M70 in healthy human volunteers potently reduces serum levels of 7?-hydroxy-4-cholesten-3-one, a surrogate marker for the hepatic activity of cholesterol 7?-hydroxylase (CYP7A1), the enzyme responsible for catalyzing the first and rate-limiting step in the classical bile acid synthetic pathway. This study provides direct evidence for the regulation of bile acid metabolism by FGF19 pathway in humans. On the basis of these results, the development of nontumorigenic FGF19 variants capable of modulating CYP7A1 expression represents an effective approach for the prevention and treatment of cholestatic liver diseases as well as potentially for other disorders associated with bile acid dysregulation.
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LMO4 functions as a negative regulator of sensory organ formation in the mammalian cochlea.
J. Neurosci.
PUBLISHED: 07-25-2014
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In mammals, formation of the auditory sensory organ (the organ of Corti) is restricted to a specialized area of the cochlea. However, the molecular mechanisms limiting sensory formation to this discrete region in the ventral cochlear duct are not well understood, nor is it known whether other regions of the cochlea have the competence to form the organ of Corti. Here we identify LMO4, a LIM-domain-only nuclear protein, as a negative regulator of sensory organ formation in the cochlea. Inactivation of Lmo4 in mice leads to an ectopic organ of Corti (eOC) located in the lateral cochlea. The eOC retains the features of the native organ, including inner and outer hair cells, supporting cells, and other nonsensory specialized cell types. However, the eOC shows an orientation opposite to the native organ, such that the eOC appears as a mirror-image duplication to the native organ of Corti. These data demonstrate a novel sensory competent region in the lateral cochlear duct that is regulated by LMO4 and may be amenable to therapeutic manipulation.
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Failure of replicating the association between hippocampal volume and 3 single-nucleotide polymorphisms identified from the European genome-wide association study in Asian populations.
Neurobiol. Aging
PUBLISHED: 07-19-2014
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Hippocampal volume is a key brain structure for learning ability and memory process, and hippocampal atrophy is a recognized biological marker of Alzheimer's disease. However, the genetic bases of hippocampal volume are still unclear although it is a heritable trait. Genome-wide association studies (GWASs) on hippocampal volume have implicated several significantly associated genetic variants in Europeans. Here, to test the contributions of these GWASs identified genetic variants to hippocampal volume in different ethnic populations, we screened the GWAS-identified candidate single-nucleotide polymorphisms in 3 independent healthy Asian brain imaging samples (a total of 990 subjects). The results showed that none of these single-nucleotide polymorphisms were associated with hippocampal volume in either individual or combined Asian samples. The replication results suggested a complexity of genetic architecture for hippocampal volume and potential genetic heterogeneity between different ethnic populations.
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Convergent heteroditopic cyclo[6]aramides as macrocyclic ion-pair receptors for constructing [2]pseudorotaxanes.
Chem. Commun. (Camb.)
PUBLISHED: 06-12-2014
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A strategy of using amide groups as the only functionality was developed to construct convergent heteroditopic cyclo[6]aramides that are able to strongly bind dibutylammonium chloride in chloroform (>10(5) M(-1)), leading to the formation of [2]pseudorotaxanes.
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[Clinical analysis of heterozygous ABCA3 mutations in children].
Zhonghua Er Ke Za Zhi
PUBLISHED: 06-12-2014
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To investigate the association of ATP-binding cassette transporter A3 (ABCA3) gene mutations with severe neonatal respiratory distress syndrome (NRDS) and lung disease in children.
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A new Lycopodium alkaloid from Phlegmariurus fargesii.
Chin J Nat Med
PUBLISHED: 05-27-2014
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To investigate the chemical constituents from the whole plants of Phlegmariurus fargesii.
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Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children.
BMC Infect. Dis.
PUBLISHED: 05-09-2014
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Human bocavirus is a newly discovered parvovirus. Multiple studies have confirmed the presence of human bocavirus1 (HBoV1) in respiratory tract samples of children. The viral load, presentation of single detection and its role as a causative agent of severe respiratory tract infections have not been thoroughly elucidated.
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Optimization of GPR40 Agonists for Type 2 Diabetes.
ACS Med Chem Lett
PUBLISHED: 05-08-2014
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GPR40 (FFA1 and FFAR1) has gained significant interest as a target for the treatment of type 2 diabetes. TAK-875 (1), a GPR40 agonist, lowered hemoglobin A1c (HbA1c) and lowered both postprandial and fasting blood glucose levels in type 2 diabetic patients in phase II clinical trials. We optimized phenylpropanoic acid derivatives as GPR40 agonists and identified AMG 837 (2) as a clinical candidate. Here we report our efforts in searching for structurally distinct back-ups for AMG 837. These efforts led to the identification of more polar GPR40 agonists, such as AM-4668 (10), that have improved potency, excellent pharmacokinetic properties across species, and minimum central nervous system (CNS) penetration.
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Teucvisins A-E, five new neo-clerodane diterpenes from Teucrium viscidum.
Chem. Pharm. Bull.
PUBLISHED: 05-03-2014
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Two new neo-clerodane diterpenoids, teucvisins A and B (1, 2), and three new 19-nor-neoclerodane diterpenoids, teucvisins C-E (3-5), together with ten known constituents (6-15) were isolated from the whole plants of Teucrium viscidum. All the isolates were evaluated for their inhibitory activities of lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 macrophages. The results indicated that compounds 11 and 15 showed moderate inhibition with an IC50 value of 21.9 and 22.4?µM, respectively.
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Polymorphisms of leptin-b gene associated with growth traits in orange-spotted grouper (Epinephelus coioides).
Int J Mol Sci
PUBLISHED: 04-25-2014
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In mammals, leptin has been demonstrated to perform important roles in many physiological activities and to influence development, growth, metabolism and reproduction. However, in fish, its function is still unclear. Duplicate leptin genes, leptin-a and leptin-b, have been identified in the orange-spotted grouper. In the present study, the polymorphisms in the leptin-b gene of the orange-spotted grouper were detected, and the relation between these polymorphisms and 12 growth traits were analyzed. Six polymorphisms (including 3 single nucleotide polymorphisms (c.14G>A, c.93A>G, c.149G>A) in exon 1, 2 SNPs (c.181A>G, c.193G>A) in intron 1, and 1 SNP (c.360C>T) in exon 2) were identified and genotyped from 200 different individuals. The results revealed that the SNP c.149G>A was significantly associated with growth traits, that the heterozygous mutation genotype GA having negative effects on growth traits. However, the other five SNPs (c.14G>A, c.93A>G, c.181A>G, c.193G>A, c.360C>T) did not show significant associations with all the growth traits. Compared with our findings in leptin-a gene, the results suggested that the leptin-a hormone has more important physiological effects in fish bodies than the leptin-b type. Moreover, leptin genes were supposed to be one class of major candidate genes of regulating growth traits in the orange-spotted grouper.
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Decreased plasma neuroactive amino acids and increased nitric oxide levels in melancholic major depressive disorder.
BMC Psychiatry
PUBLISHED: 04-22-2014
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Amino acid neurotransmitters and nitric oxide (NO) are involved in the pathogenesis of major depressive disorder (MDD). Here we want to establish whether changes in their plasma levels may serve as biomarker for the melancholic subtype of this disorder.
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Monoterpenes from the fruits of Amomum kravanh.
J Asian Nat Prod Res
PUBLISHED: 04-22-2014
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Two new monoterpenes, (7S)-p-cymene-2,7,8-triol (1) and (3R,4R,6S)-p-menth-1-ene-3,6,10-triol (2), were isolated from the fruits of Amomum kravanh. Their structures were established by spectroscopic data. The absolute configuration of the 7,8-diol moiety in 1 was assigned by CD data after addition of Mo2(OAc)4 in dimethyl sulfoxide (DMSO) solution. Compounds 1 and 2 exhibited weak activity of anti-platelet aggregation in vitro.
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Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder.
Psychoneuroendocrinology
PUBLISHED: 04-14-2014
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Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (P<0.001). Plasma CORT levels were increased in male CUS rats (P=0.001), while male MDD patients did not show a significant change in cortisol levels. In conclusion, the changes in plasma and hypothalamic NOS-NO of CUS rats and MDD were similar. The male CUS rat model may thus help us with our investigation of the mechanism underlying NOS-NO alterations in depression.
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Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists.
ACS Med Chem Lett
PUBLISHED: 04-10-2014
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We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.
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Can non-invasive positive pressure ventilation prevent endotracheal intubation in acute lung injury/acute respiratory distress syndrome? A meta-analysis.
Respirology
PUBLISHED: 03-26-2014
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The role of non-invasive positive pressure ventilation (NIPPV) in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is controversial. The aim of this study was to investigate whether NIPPV could prevent endotracheal intubation and decrease mortality rate in patients with ALI/ARDS. Randomized controlled trials (RCT) which reported endotracheal intubation and mortality rate in patients with ALI/ARDS treated by NIPPV were identified in Pubmed, Medline, Embase, Central Cochrane Controlled Trials Register, Chinese National Knowledge Infrastructure, reference lists and by manual searches. Fixed- and random-effects models were used to calculate pooled relative risks. This meta-analysis included six RCT involving 227 patients. The results showed that endotracheal intubation rate was lower in NIPPV (95% confidence interval (CI): 0.44-0.80, z?=?3.44, P?=?0.0006), but no significant difference was found either in intensive care unit (ICU) mortality (95% CI: 0.45-1.07, z?=?1.65, P?=?0.10) or in hospital mortality (95% CI: 0.17-1.58, z?=?1.16, P?=?0.25). Only two studies discussed the aetiology of ALI/ARDS as pulmonary or extra-pulmonary, and neither showed statistical heterogeneity (I(2) ?=?0%, ?(2) ?=?0.31, P?=?0.58), nor a significant difference in endotracheal intubation rate (95% CI: 0.35-9.08, z?=?0.69, P?=?0.49). In conclusion, the early use of NIPPV can decrease the endotracheal intubation rate in patients with ALI/ARDS, but does not change the mortality of these patients.
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Cytotoxic polycyclic polyprenylated acylphloroglucinols from Hypericum attenuatum.
Fitoterapia
PUBLISHED: 02-18-2014
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Six new polycyclic polyprenylated acylphloroglucinols, attenuatumiones A-F (1-6), together with twelve known analogs (7-18) were isolated from the whole plant of Hypericum attenuatum. Their structures were elucidated by spectroscopic methods, and the absolute configuration of C-13 in attenuatumione C (3) was deduced via the circular dichroism datum of the in situ formed [Rh2(OCOCF3)4] complexes. All isolates were evaluated for the cytotoxic activities on three human cancer cell lines. Compound 3 showed moderate cytotoxic activities with IC50 values of 10.12 and 10.56 ?M against SMMC7721 and U2OS, respectively.
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Optimization of 2-(3-(arylalkyl amino carbonyl) phenyl)-3-(2-methoxyphenyl)-4-thiazolidinone derivatives as potent antitumor growth and metastasis agents.
Eur J Med Chem
PUBLISHED: 02-16-2014
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A series of 2,3-diaryl-4-thiazolidinone derivatives were synthesized and evaluated for their antiproliferative properties against two well-known cancer cell lines (A549 as human lung cancer and MDA-MB-231 as human breast cancer). Structure activity relationship (SAR) analysis resulted in the discovery of 2-(3-(arylalkyl amino carbonyl)phenyl)-3-(2-methoxy-phenyl)-4-thiazolidinone derivatives with high potent inhibitory effects on the proliferation of both cancer cell lines. Furthermore, several compounds with potent antiproliferative activities displayed excellent inhibitory activities on migration with an IC50 of about 0.05 ?M on MDA-MB-231 cells in two different migration assays. In particular, compound 39 was indicated to suppress tumor growth and metastasis as well as promote survival rate. Intriguingly, this series of analogs have been indicated to inhibit tumor cell proliferation through inducing cell cycle arrest. These results suggested that the new series of 2-(3-(arylalkyl amino carbonyl)phenyl)-3-(2-methoxyphenyl)-4-thiazolidinone derivatives could be regarded and developed as novel highly potential anticancer agents in the future.
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Clustering of surface NMDA receptors is mainly mediated by the C-terminus of GluN2A in cultured rat hippocampal neurons.
Neurosci Bull
PUBLISHED: 02-14-2014
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N-methyl-D-aspartate receptors (NMDARs) containing different GluN2 subunits play distinct roles in synaptic plasticity. Such differences may not only be determined by the channel properties, but also by differential surface distribution and synaptic localization.In the present study, using a Cy3-conjugated Fab fragment of the GFP antibody to label surface-located GluN2 subunits tagged with GFP at the N-terminus,we observed the membrane distribution patterns of GluN2A- or GluN2B-containing NMDARs in cultured rat hippocampal neurons. We found that surface NMDARs containing GluN2A, but not those containing GluN2B,were inclined to cluster at DIV7. Swapping the carboxyl termini of the GluN2 subunits completely reversed these distribution patterns. In addition, surface NMDARs containing GluN2A were preferentially associated with PSD-95. Taken together, the results of our study suggest that the clustering distribution of GluN2A containing NMDARs is determined by the GluN2AC-terminus, and its interaction with PSD-95 plays animportant role in this process.
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Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.
Nat. Med.
PUBLISHED: 02-08-2014
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As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts--in which circulatory systems of young and aged animals are connected--identified synaptic plasticity-related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.
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Antihyperglycemic glucosylated coumaroyltyramine derivatives from Teucrium viscidum.
J. Nat. Prod.
PUBLISHED: 01-31-2014
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Eight new glucosylated coumaroyltyramine derivatives, teuvissides A-H (1-8), were isolated from whole plants of Teucrium viscidum. Their structures were elucidated using spectroscopic data and chemical methods. The antihyperglycemic activities of these compounds were evaluated in HepG2 cells and 3T3-L1 adipocytes, and all of the isolates elicited different levels of glucose consumption at a concentration of 2.0 ?M. Teuvissides A (1), B (2), and F (6) induced 2.2-, 2.1-, and 2.2-fold changes, respectively, in the levels of glucose consumption in HepG2 cells and 2.5-, 2.1-, and 2.3-fold changes, respectively, in 3T3-L1 adipocytes relative to the basal levels.
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Maternal exposure to bisphenol A may increase the risks of Parkinson's disease through down-regulation of fetal IGF-1 expression.
Med. Hypotheses
PUBLISHED: 01-29-2014
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So far, the pathogenesis of Parkinson's disease (PD) remains unclear. Current studies implicate environmental toxins may be potential causes of fetal origin of PD. BPA is a member of the family of estrogenic chemicals existing widely in environment. Significant evidences from animal experimentation have demonstrated that BPA interfere with fetal neurodevelopment. Based on previous reports and our research on EB derived from hESCs, we speculate that maternal exposure to low-dose BPA during gestational period may decrease IGF-1 expression, thus hinder the development of fetal DA neurons, and finally increase the risks of fetal origin of PD. Our hypothesis may shed new light on the pathogenesis of PD and lead to potential preventive treatments.
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Withanolides from Physalis minima and their inhibitory effects on nitric oxide production.
Steroids
PUBLISHED: 01-11-2014
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Six new withanolides (1-6), including two uncommon 1,10-seco withanolides (1 and 2), together with five known withanolides (7-11), were isolated from the whole plants of Physalis minima Linn.. The structures of new compounds were elucidated through spectroscopic methods, including (1)H, (13)C NMR, 2D-NMR, HRESIMS and circular dichroism (CD). Inhibitory effects of the isolates on nitric oxide (NO) production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated. Compounds 2 and 5 showed strong inhibitory activities with IC50 values of 8.04 and 10.01 ?M, respectively. Compounds 1, 9 and 10 exhibited moderate inhibitory activities with IC50 values from 25.54 to 43.58 ?M.
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Comparison of the Efficacy of Rosuvastatin versus Atorvastatin in Preventing Contrast Induced Nephropathy in Patient with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.
PLoS ONE
PUBLISHED: 01-01-2014
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We prospectively compared the preventive effects of rosuvastatin and atorvastatin on contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI).
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Clinical features of airway malacia in children: a retrospective analysis of 459 patients.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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To investigate the clinical features of airway malacia in children.
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Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines.
Beilstein J Org Chem
PUBLISHED: 01-01-2014
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A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine's synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99:1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.
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[Population structure and spatial distribution pattern of Camellia azalea in E huangzhang Nature Reserve of Guangdong, China].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 12-31-2013
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This paper studied the structures of basal diameter, height and canopy width of Camellia azalea population in E huangzhang Nature Reserve of Guangdong. The spatial distribution patterns and dynamics of the population were measured by applying aggregate indices including disperse coefficient, negative binomial distribution, Cassie index, clumping index, mean crowding, patch index and Green index. The results showed that in the natural distribution region, the population was mainly composed of adult trees, and was in declining due to seriously lack of seedlings. The structures of diameter, height and canopy width were not identical among different plots. In the plots, the spatial distribution pattern of C. azalea population showed clump or random, and changed from clump to random with the development of the population.
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[Clinical features and prognosis in 104 colorectal cancer patients with bone metastases].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 12-30-2013
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To investigate the clinical features and prognosis of bone metastases in colorectal cancer patients.
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Development of GABA Circuitry of Fast-Spiking Basket Interneurons in the Medial Prefrontal Cortex of erbb4-Mutant Mice.
J. Neurosci.
PUBLISHED: 12-17-2013
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erbb4 is a susceptibility gene for schizophrenia and ErbB4 signals have been hypothesized to function in a number of cortical developmental processes (Silberberg et al., 2006; Mei and Xiong, 2008). Several recent studies show that the expression of ErbB4 is mainly restricted to GABAergic interneurons (Yau et al., 2003; Woo et al., 2007), specifically, to parvalbumin-positive (PV) fast-spiking (FS) interneurons (Vullhorst et al., 2009; Fazzari et al., 2010), a large majority of which are PV FS basket cells (Kawaguchi, 1995; Taniguchi et al., 2013). However, in the medial prefrontal cortex (mPFC), a brain region that is closely associated with neuropsychiatric disorders including schizophrenia, little is known about the roles of ErbB4 signals during the development of GABAergic circuitry particularly that associated with PV FS basket cells. Here, using molecular genetics, biochemistry, and electrophysiology, we deleted ErbB4 receptors in GABAergic forebrain neurons during the embryonic period and demonstrated that in the mouse mPFC, ErbB4 signals were dispensable for the development of GABAergic synapses by PV FS basket cells. Interestingly, they were required for the final maturation rather than the initial formation of glutamatergic synapses on PV FS basket cells. Furthermore, activity-dependent GABAergic PV FS pyramidal neuron transmission was decreased, whereas activity of pyramidal neurons was increased in KO mice. Together, these data indicate that ErbB4 signals contribute to the development of GABAergic circuitry associated with FS basket cells in component- and stage-dependent manners in the mPFC in vivo, and may suggest a mechanism for neuropsychiatric disorders including schizophrenia.
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Bioactive Benzofuran Neolignans from Aristolochia fordiana.
Planta Med.
PUBLISHED: 11-28-2013
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Six new benzofuran neolignans (1-6) were isolated from the EtOAc-soluble fraction of the aerial part of Aristolochia fordiana, together with twelve known analogues (7-18). The structures of the isolated compounds were elucidated by spectroscopic methods. All isolates were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccaride-activated RAW264.7 macrophages and for their cytotoxic activities on three human cancer cell lines. Compound 2 showed significant nitric oxide production inhibitory activity with an IC50 value of 10.00?µM, while compound 16 exhibited cytotoxic activity with an IC50 value of 11.9?µM against MG-63 and compound 18 of 9.15?µM against HepG2 cell lines, respectively.
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Changes of cerebrospinal fluid pressure after thoracic endovascular aortic repair.
Chin. Med. J.
PUBLISHED: 11-16-2013
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Decreasing the intracranial pressure has been advocated as one of the major protective strategies to prevent spinal cord ischemia after endovascular aortic repair. However, the actual changes of cerebrospinal fluid (CSF) pressure and its relation with spinal cord ischemia have been poorly understood. We performed CSF pressure measurements and provisional CSF withdrawal after thoracic endovascular aortic repair, and compared the changes of CSF pressure in high risk patients and in patients with new onset paraplegia and paraparesis.
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Aphanamenes A and B, two new acyclic diterpene [4 + 2]-cycloaddition adducts from Aphanamixis grandifolia.
Org. Lett.
PUBLISHED: 10-18-2013
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Aphanamenes A (1) and B (2), two unprecedented acyclic diterpene dimers formed via a [4 + 2]-cycloaddition, were isolated from the root bark of Aphanamixis grandifolia. Their structures were elucidated by spectroscopic analyses, and the absolute configuration of 1 was determined by ECD calculations. Both 1 and 2 showed significant inhibition on NO production on lipopolysaccharide-induced RAW264.7 macrophages.
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[Clinical analysis of 28 cases of bronchiolitis obliterans].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 10-18-2013
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To study the clinical features of bronchiolitis obliterans (BO) in children.
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[Analysis of coronary rotational atherectomy related complications].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 10-12-2013
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To analysis the complications of coronary rotational atherectomy and evaluate the safety of this procedure.
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[Risk factors for massive ascites after living donor liver transplantation in adult and impact of massive ascites on patient survival].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 09-25-2013
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To analyze the risk factors relate to massive ascites after the living donor liver transplantation (LDLT) in adult and the impact of massive ascites on patient survival.
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Nonaggregational shape-persistent cyclo[6]aramide and its macrocyclic effect toward binding secondary ammonium salts in moderately polar media.
Org. Lett.
PUBLISHED: 09-11-2013
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Simply by introducing steric side chains, the shape-persistent cyclo[6]aramides were found to exhibit nonaggregational behavior and strong association (3 × 10(4) M(-1)) ability in acetone for binding secondary ammonium salt. The complexation can be switched in an on-and-off fashion using AgPF6 and TBACl, contrasting sharply with their corresponding acyclic pentamer and demonstrating the macrocyclic effect.
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GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the G?q-p63RhoGEF-Rho GTPase pathway.
Cancer Res.
PUBLISHED: 09-05-2013
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Adhesion G-protein-coupled receptors (GPCR), which contain adhesion domains in their extracellular region, have been found to play important roles in cell adhesion, motility, embryonic development, and immune response. Because most adhesion molecules with adhesion domains have vital roles in cancer metastasis, we speculated that adhesion GPCRs are potentially involved in cancer metastasis. In this study, we identified GPR116 as a novel regulator of breast cancer metastasis through expression and functional screening of the adhesion GPCR family. We found that knockdown of GPR116 in highly metastatic (MDA-MB-231) breast cancer cells suppressed cell migration and invasion. Conversely, ectopic GPR116 expression in poorly metastatic (MCF-7 and Hs578T) cells promoted cell invasion. We further showed that knockdown of GPR116 inhibited breast cancer cell metastasis in two mammary tumor metastasis mouse models. Moreover, GPR116 modulated the formation of lamellipodia and actin stress fibers in cells in a RhoA- and Rac1-dependent manner. At a molecular level, GPR116 regulated cell motility and morphology through the G?q-p63RhoGEF-RhoA/Rac1 pathway. The biologic significance of GPR116 in breast cancer is substantiated in human patient samples, where GPR116 expression is significantly correlated with breast tumor progression, recurrence, and poor prognosis. These findings show that GPR116 is crucial for the metastasis of breast cancer and support GPR116 as a potential prognostic marker and drug target against metastatic human breast cancer.
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Geranylated 2-arylbenzofurans from Morus alba var. tatarica and their ?-glucosidase and protein tyrosine phosphatase 1B inhibitory activities.
Fitoterapia
PUBLISHED: 08-22-2013
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Ten new geranylated 2-arylbenzofuran derivatives, including two monoterpenoid 2-arylbenzofurans (1 and 2), two geranylated 2-arylbenzofuran enantiomers (3a and 3b), and six geranylated 2-arylbenzofurans (4-9), along with four known 2-arylbenzofurans (10-13) were isolated from the root bark of Morus alba var. tatarica. Their structures and relative configurations were established on the basis of spectroscopic data analysis. Compounds 3-7 with one asymmetric carbon at C-7? were supposed to be enantiomeric mixtures confirmed by chiral HPLC analysis, and the absolute configurations of each enantiomer in 3-7 were determined by Rh2(OCOCF3)4-induced CD and Snatzkes method. The enantiomers with the substituting group at C-2 exhibited better resolutions on a Chiralpak AD-H column than those with the substituting group at C-4. Compounds 1-7, 10, 11 and 13, showed ?-glucosidase inhibitory activities with IC50 values of 11.9-131.9?M, and compounds 1 and 9-13 inhibited protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 7.9-38.1?M.
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Chemical characteristics combined with bioactivity for comprehensive evaluation of Panax ginseng C.A. Meyer in different ages and seasons based on HPLC-DAD and chemometric methods.
J Pharm Biomed Anal
PUBLISHED: 08-06-2013
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Panax ginseng C.A. Meyer has been known as a valuable traditional Chinese medicines for thousands years of history. Ginsenosides, the main active constituents, exhibit prominent immunoregulation effect. The present study first describes a holistic method based on chemical characteristic and lymphocyte proliferative capacity to evaluate systematically the quality of P. ginseng in thirty samples from different seasons during 2-6 years. The HPLC fingerprints were evaluated using principle component analysis (PCA) and hierarchical clustering analysis (HCA). The spectrum-efficacy model between HPLC fingerprints and T-lymphocyte proliferative activities was investigated by principal component regression (PCR) and partial least squares (PLS). The results indicated that the growth of the ginsenosides could be grouped into three periods and from August of the fifth year, P. ginseng appeared significant lymphocyte proliferative capacity. Close correlation existed between the spectrum-efficacy relationship and ginsenosides Rb1, Ro, Rc, Rb2 and Re were the main contributive components to the lymphocyte proliferative capacity. This comprehensive strategy, providing reliable and adequate scientific evidence, could be applied to other TCMs to ameliorate their quality control.
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Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice.
Dev. Dyn.
PUBLISHED: 07-25-2013
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Background: BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid-releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5s functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas. Results: In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. Conclusions: Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes. Developmental Dynamics, 2013. © 2013 Wiley Periodicals, Inc.
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Upregulation of glutamate transporter GLT-1 by mTOR-Akt-NF-?B cascade in astrocytic oxygen-glucose deprivation.
Glia
PUBLISHED: 07-24-2013
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Excessive extracellular glutamate leads to neuronal death in central nervous system. Excitatory glutamate transporter subtype 2 (GLT-1) carries bulk of glutamate reuptake in cerebral ischemia. Although GLT-1 expression fluctuates during the period of ischemia, little is known about its regulatory mechanism. Here we show an up-regulation of GLT-1 via mammalian target of rapamycin (mTOR)-Akt-nuclear factor-?B (NF-?B) signaling cascade in oxygen glucose deprivation (OGD). We found that brief rapamycin treatment significantly increased GLT-1 expression in cultured astrocytes. Rapamycin increased phosphorylation of raptor at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1 expression. This conclusion was further confirmed by raptor and rictor disruption experiments. Akt was activated by mTORC1 inhibition and required for GLT-1 expression because triciribine, a specific inhibitor of Akt, blocked the increase of GLT-1 expression. mTOR-Akt cascade then activated NF-?B and increased ?B-motif-binding phosphoprotein (KBBP) expression and GLT-1 transcription. We next demonstrated that mTOR-Akt-NF-?B cascade was activated in OGD and subsequently caused the upregulation of GLT-1. Supporting evidence included: (1) inhibition of Akt or NF-?B occluded OGD-induced GLT-1 upregulation; (2) Raptor knock-down plus OGD did not add to the increase of GLT-1 expression; (3) Intact mTORC2 was required for GLT-1 enhancement. In summary, our data first showed that mTOR-Akt-NF-?B cascade played critical roles to up-regulate GLT-1 in OGD. This signaling cascade may work to promote glutamate uptake in brain ischemia and neurodegenerative diseases.
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Different apoptotic effects of triterpenoid saponin-rich Gypsophila oldhamiana root extract on human hepatoma SMMC-7721 and normal human hepatic L02 cells.
Biol. Pharm. Bull.
PUBLISHED: 07-02-2013
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The roots of Gypsophila oldhamiana are rich in triterpenoid saponins with antitumor properties. Although previous reports have revealed the anticancer potency of some Gypsophila species, the underlying molecular mechanisms of this activity have not been studied in detail. The purpose of the present study was to prepare a triterpenoid saponin-rich G. oldhamiana root extract (TGOE) determined by LC-electrospray ionization (ESI)-MS(n) for biological studies and to evaluate the different anti-proliferative activities and apoptotic effects of TGOE on human hepatoma SMMC-7721 and normal human hepatic L02 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that TGOE selectively inhibited the proliferation of SMMC-7721 cells in a dose-dependent manner with IC50 value of 19.50±3.63?µg/mL, while the cytotoxic effects of TGOE on L02 cells were much lower with IC50 value of 40.48±3.74?µg/mL. Analysis of apoptotic morphological changes and flow cytometry indicated that TGOE might preferentially induce apoptosis in SMMC-7721 cells, while exhibited much lower effects on L02 cells. Western blot analysis showed that the different apoptotic effects of TGOE on SMMC-7721 and L02 cells were due to different protein regulation of caspase-3 and mitogen activated protein kinases (MAPKs). TGOE significantly activated caspase-3 and increased the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), while decreased the phosphorylation of p38 in SMMC-7721 cells. However, the expression of these proteins was not statistically changed in L02 cells, except for the up-regulation of p38 phosphorylation. These results suggest that TGOE may have potential beneficial effects against hepatocellular carcinoma.
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Construction of high-density genetic linkage maps for orange-spotted grouper Epinephelus coioides using multiplexed shotgun genotyping.
BMC Genet.
PUBLISHED: 06-23-2013
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Orange-spotted grouper, Epinephelus coioides, is one of the most valuable fish species in China. Commercial production of orange-spotted grouper could be increased by developing higher growth rates and improving commercially important traits. Information on genetic markers associated with quantitative trait loci (QTL) can be used in breeding programs to identify and select individuals carrying desired traits. A high-density genetic linkage map is the basis for QTL study, and multiplexed shotgun genotyping (MSG) facilitates the development of single nucleotide polymorphisms (SNPs) and genotyping. In this study, the first high-density genetic linkage maps for groupers were generated on the basis of the MSG method.
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A pair of sulfonated diarylheptanoid epimers from Kaempferia galanga.
Chin J Nat Med
PUBLISHED: 06-22-2013
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To discover new bioactive constituents from Kaempferia galanga L. (Zingiberaceae).
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Surge block method for controlling well clogging and sampling sediment during bioremediation.
Water Res.
PUBLISHED: 05-24-2013
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A surge block treatment method (i.e. inserting a solid rod plunger with a flat seal that closely fits the casing interior into a well and stocking it up and down) was performed for the rehabilitation of wells clogged with biomass and for the collection of time series sediment samples during in situ bioremediation tests for U(VI) immobilization at a the U.S. Department of Energy site in Oak Ridge, TN. The clogging caused by biomass growth had been controlled by using routine surge block treatment for 18 times over a nearly four year test period. The treatment frequency was dependent of the dosage of electron donor injection and microbial community developed in the subsurface. Hydraulic tests showed that the apparent aquifer transmissivity at a clogged well with an inner diameter (ID) of 10.16 cm was increased by 8-13 times after the rehabilitation, indicating the effectiveness of the rehabilitation. Simultaneously with the rehabilitation, the surge block method was successfully used for collecting time series sediment samples composed of fine particles (clay and silt) from wells with ID 1.9-10.16 cm for the analysis of mineralogical and geochemical composition and microbial community during the same period. Our results demonstrated that the surge block method provided a cost-effective approach for both well rehabilitation and frequent solid sampling at the same location.
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An increase in synaptic NMDA receptors in the insular cortex contributes to neuropathic pain.
Sci Signal
PUBLISHED: 05-16-2013
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Neurons in the insular cortex are activated by acute and chronic pain, and inhibition of neuronal activity in the insular cortex has analgesic effects. We found that in a mouse model in which peripheral nerve injury leads to the development of neuropathic pain, the insular cortex showed changes in synaptic plasticity, which were associated with a long-term increase in the amount of synaptic N-methyl-d-aspartate receptors (NMDARs), but not that of extrasynaptic NMDARs. Activation of cyclic adenosine monophosphate (cAMP)-dependent signaling enhanced the amount of synaptic NMDARs in acutely isolated insular cortical slices and increased the surface localization of NMDARs in cultured cortical neurons. We found that the increase in the amount of NMDARs required phosphorylation of the NMDAR subunit GluN2B at Tyr(1472) by a pathway involving adenylyl cyclase subtype 1 (AC1), protein kinase A (PKA), and Src family kinases. Finally, injecting NMDAR or GluN2B-specific antagonists into the insular cortex reduced behavioral responses to normally nonnoxious stimuli in the mouse model of neuropathic pain. Our results suggest that activity-dependent plasticity takes place in the insular cortex after nerve injury and that inhibiting the increase in NMDAR function may help to prevent or treat neuropathic pain.
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GATA3 controls the specification of prosensory domain and neuronal survival in the mouse cochlea.
Hum. Mol. Genet.
PUBLISHED: 05-10-2013
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HDR syndrome (also known as Barakat syndrome) is a developmental disorder characterized by hypoparathyroidism, sensorineural deafness and renal disease. Although genetic mapping and subsequent functional studies indicate that GATA3 haplo-insufficiency causes human HDR syndrome, the role of Gata3 in sensorineural deafness and auditory system development is largely unknown. In this study, we show that Gata3 is continuously expressed in the developing mouse inner ear. Conditional knockout of Gata3 in the developing inner ear disrupts the morphogenesis of mouse inner ear, resulting in a disorganized and shortened cochlear duct with significant fewer hair cells and supporting cells. Loss of Gata3 function leads to the failure in the specification of prosensory domain and subsequently, to increased cell death in the cochlear duct. Moreover, though the initial generation of cochleovestibular ganglion (CVG) cells is not affected in Gata3-null mice, spiral ganglion neurons (SGNs) are nearly depleted due to apoptosis. Our results demonstrate the essential role of Gata3 in specifying the prosensory domain in the cochlea and in regulating the survival of SGNs, thus identifying a molecular mechanism underlying human HDR syndrome.
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Perioperative aortic dissection rupture after endovascular stent graft placement for treatment of type B dissection.
Chin. Med. J.
PUBLISHED: 05-09-2013
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The perioperative aortic dissection (AD) rupture is a severe event after endovascular stent graft placement for treatment of type B AD. However, this life-threatening complication has not undergone systematic investigation. The aim of the study is to discuss the reasons of AD rupture after the procedure.
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Three new Lycopodium alkaloids from Lycopodium obscurum.
J Asian Nat Prod Res
PUBLISHED: 04-22-2013
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Chemical investigation on the crude alkaloid portion of Lycopodium obscurum led to isolation of three new fawcettimine-type Lycopodium alkaloids, lycobscurines A-C (1-3), together with three known compounds. Their structures were determined by spectroscopic methods including HR-ESI-MS and NMR techniques. All compounds were tested in an assay for acetylcholinesterase inhibitory activity.
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GluN2A versus GluN2B: twins, but quite different.
Neurosci Bull
PUBLISHED: 04-20-2013
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N-Methyl-D-aspartate receptors (NMDARs) play vital roles in the central nervous system, as they are primary mediators of Ca(2+) influx during synaptic activity. The subunits that compose NMDARs share similar topological structures but are distinct in distribution and pharmacological properties, as well as physiological and pathological functions, which make the NMDAR one of the most complex and elusive ionotropic glutamate receptors. In this review, we focus on GluN2A and GluN2B, the primary NMDAR subunits in the cortex and hippocampus, and discuss their differences in developmental expression, brain distribution, trafficking, and functional properties during neuronal activity.
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Cysteine residues 87 and 320 in the amino terminal domain of NMDA receptor GluN2A govern its homodimerization but do not influence GluN2A/GluN1 heteromeric assembly.
Neurosci Bull
PUBLISHED: 04-20-2013
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N-Methyl-D-aspartate receptors (NMDARs) play a central role in various physiological and pathological processes in the central nervous system. And they are commonly composed of four subunits, two GluN1 subunits and two GluN2 or GluN3 subunits. The different subunit compositions make NMDARs a heterogeneous population with distinct electrophysiological and pharmacological properties and thus with different abilities to conduct neuronal activities. The subunit composition, assembly process, and final structure of assembled NMDARs have been studied for years but no consensus has been achieved. In this study, we investigated the role of the amino terminal domain (ATD) of GluN2A in regulating NMDAR assembly. The ATD of GluN2A was first expressed in heterogeneous cells and the homodimer formation was investigated by fluorescent resonance energy transfer and non-reducing SDSPAGE electrophoresis. Each of the three cysteine residues located in the ATD was mutated into alanine, and the homodimerization of the ATD or GluN2A, as well as the heteromeric assembly of NMDARs was assessed by non-reducing SDSPAGE electrophoresis, co-immunoprecipitation and immunocytochemistry. We found that two cysteine residues, C87 and C320, in the ATD of the GluN2A subunit were required for the formation of disulfide bonds and GluN2A ATD homodimers. Furthermore, the disruption of GluN2A ATD domain dimerization had no influence on the assembly and surface expression of NMDARs. These results suggest that the two ATD domains of GluN2A are structurally adjacent in fully-assembled NMDARs. However, unlike GluN1, the homomerization of the ATD domain of GluN2A is not required for the assembly of NMDARs, implying that GluN2A and GluN1 play unequal roles in NMDAR assembly.
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Six new cyclic peptides from the roots of Gypsophila oldhamiana.
Chem. Pharm. Bull.
PUBLISHED: 04-03-2013
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Six new cyclic peptides, gypsophin A-F (1-6), were isolated from Gypsophila oldhamiana. Their structures were elucidated by extensive NMR and chemical degradation. Compound 3 exhibited moderate activity of antiplatelet aggregation in vitro.
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Risk factors of late-onset neonatal sepsis in Taiwan: A matched case-control study.
J Microbiol Immunol Infect
PUBLISHED: 03-14-2013
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Infants in a neonatal intensive care unit (NICU) have a higher incidence of bloodstream infections (BSIs) than any other pediatric or adult population. The predisposing factors have not been comprehensively evaluated in this population in Taiwan.
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Amomaxins A and B, two unprecedented rearranged labdane norditerpenoids with a nine-membered ring from Amomum maximum.
Org. Lett.
PUBLISHED: 03-08-2013
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Amomaxins A (1) and B (2), featuring an unprecedented rearranged labdane norditerpene skeleton with a nine-membered ring, along with their biosynthetic related known compound isocoronarin D (3) were isolated from the roots of Amomum maximum. Their structures with absolute configurations were determined by spectroscopic data, CD experimentation, and single-crystal X-ray diffraction. Compound 2 showed an inhibitory effect on nitric oxide (NO) production in lipopolysaccharide-induced RAW264.7 macrophages.
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Tetracyclic diterpenoids with isomerized isospongian skeleton and labdane diterpenoids from the fruits of Amomum kravanh.
J. Nat. Prod.
PUBLISHED: 02-08-2013
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Four novel diterpenoids, including three tetracyclic diterpenes with isomerized isospongian skeletons, kravanhins A-C (1-3), and kravanhin D (4), and three new labdane diterpenes (5-7) were isolated from the fruits of Amomum kravanh. Compounds 1-4 had unprecedented isospongian diterpene skeletons with a trans-anti-cis fused tricyclic ring system. The structures of compounds 1-7 were established on the basis of extensive analysis of NMR spectra, CD, and X-ray crystallography. Compound 2 showed inhibitory activity on nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with an IC(50) value of 36.2 ?M.
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Developmental changes in the composition of five anthraquinones from Rheum palmatum as quantified by (1) H-NMR.
Phytochem Anal
PUBLISHED: 01-31-2013
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Rheum palmatum is an important traditional Chinese medicine featuring anthraquinones with several activities. Generally, rhein, emodin, aloe-emodin, physcion and chrysophanol are used as chemical markers for the quality control of rhubarb products.
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Characterisation of homoflavonoids from three Ophioglossum species using liquid chromatography with diode array detection and electrospray ionisation tandem mass spectrometry.
Phytochem Anal
PUBLISHED: 01-29-2013
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Homoflavonoids, characterised by one more carbon atom directly added to C6 -C3 -C6 backbone of flavonoids, are rich in the species of genus Ophioglossum. Up to now we have little knowledge about their MS fragmentation patterns. It is therefore necessary to investigate their MS fragmentation pathways so as to distinguish them from other types of flavonoids.
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Sesquiterpenes from the rhizomes of Alpinia japonica and their inhibitory effects on nitric oxide production.
Fitoterapia
PUBLISHED: 01-20-2013
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A novel norsesquiterpene (1), three new bisabolenes sesquiterpenes (2-4), along with 7 known compounds (5-11), were isolated from the rhizomes of Alpinia japonica. The structures of the new compounds were elucidated by analysis of spectroscopic data. The absolute configuration of C-1 in 3 was deduced via the circular dichroism data of the in situ formed [Rh2(OCOCF3)4] complexes. Inhibitory effects of the isolates on nitric oxide production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated. Compound 6 showed significant inhibitory activity with IC50 value of 5.3 ??, and compounds 1, 3, 5 and 7-10 exhibited moderate inhibitory activities with IC50 values between 24.5 and 46.3 ?M.
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Flavonoids from Millettia nitida var. hirsutissima with their anticoagulative activities and inhibitory effects on NO production.
J Nat Med
PUBLISHED: 01-15-2013
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Two new compounds, (2R)-7,3-dihydroxy-6,4-methoxyflavan (1) and (3R)-7,4-dihydroxy-2-methoxyisoflavan (2), along with 12 known flavonoids (3-14), were isolated from the vine stems of Millettia nitida var. hirsutissima. The structures of the isolated compounds were elucidated based on spectroscopic analyses and comparison of literature data. All of the isolates were evaluated for their effects on in-vitro anticoagulative assay and on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. As a result, all compounds showed weak antiplatelet aggregation activities and compounds 4, 5, 7, 8 and 9 demonstrated antithrombin activity with a good dose-effect relationship from 5 to 100 ?g mL?¹ in rabbit plasma. Compounds 8, 9, 10 and 14 exhibited inhibitory effects on LPS-induced NO production in RAW264.7 macrophages with IC?? values of 4.79 ± 0.20, 8.23 ± 0.35, 5.23 ± 0.11 and 6.30 ± 0.30 ?g mL?¹, respectively.
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Meta-analysis indicates that the European GWAS-identified risk SNP rs1344706 within ZNF804A is not associated with schizophrenia in Han Chinese population.
PLoS ONE
PUBLISHED: 01-01-2013
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Recent genetic association studies have implicated several candidate susceptibility variants for schizophrenia among general populations. Rs1344706, an intronic SNP within ZNF804A, was identified as one of the most compelling candidate risk SNPs for schizophrenia in Europeans through genome-wide association studies (GWASs) and replications as well as large-scale meta-analyses. However, in Han Chinese, the results for rs1344706 are inconsistent, and whether rs1344706 is an authentic risk SNP for schizophrenia in Han Chinese is inconclusive. Here, we conducted a systematic meta-analysis of rs1344706 with schizophrenia in Chinese population by combining all available case-control samples (N?=?12), including a total of 8,982 cases and 12,342 controls. The results of our meta-analysis were not able to confirm an association of rs1344706 A-allele with schizophrenia (p?=?0.10, odds ratio?=?1.06, 95% confidence interval?=?0.99-1.13). Such absence of association was further confirmed by the non-superiority test (p?=?0.0003), suggesting that rs1344706 is not a risk SNP for schizophrenia in Han Chinese. Detailed examinations of individual samples revealed potential sampling bias in previous replication studies in Han Chinese. The absence of rs1344706 association in Han Chinese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating genome-wide association findings of schizophrenia across different ethnic populations.
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Synthesis and optoelectronic properties of a carbazole-modified platinum(II) complex in polymer light-emitting devices.
Dalton Trans
PUBLISHED: 11-24-2011
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To improve opto-electronic properties and efficiently suppress excimer emission, a phenylpyridine (ppy)-based platinum(II) complex (C(16)OCz-ppy)Pt(acac) was synthesized and characterized, where C(16)OCz-ppy is a 2-phenylpyridine derivative appending a carbazole moiety and three hexadecyloxy methyl units in the parent phenylpyridine, and acac is acetylacetone. This carbazole-modified platinum(II) complex exhibited good thermal stability and three times higher photoluminescent quantum yield than its parent (2-phenylpyridine-C(2),N)(2,4-pentanedionato-O,O)platinum(II) complex [(ppy)Pt(acac)]. Single-emissive-layer polymer light-emitting devices using (C(16)OC(Z)-ppy)Pt(acac) as dopant and a blend of poly(N-vinylcarbazole) and 2-(4-biphenyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole as host matrix presented a maximum current efficiency of 1.51 cd A(-1), which was 1.5 times higher than that from the (ppy)Pt(acac)-doped device with the same device structure. Little excimer emission and minor aggregation emission were observed in the (C(16)OC(Z)-ppy)Pt(acac)-doped PLEDs at different dopant concentrations and applied voltages. This work indicates that introducing a carbazole and three hexadecyloxy methyl groups into the planar platinum(II) complex can reduce molecular aggregation and excimer emissions, thus resulting in high luminance and stable EL spectra in comparison with the parent (ppy)Pt(acac).
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[Contamination mechanism and regeneration strategies of chromatographic resin in separation process for expression product from mammary gland bioreactor].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 11-22-2011
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This study focused on the contamination mechanism and regeneration strategies of sulfopropyl ion exchange resin (SP Sepharose FF) during the separation of recombinant human lactoferrin from transgenic bovine milk. We analyzed primary constituents contents in chromatorgraphic material and fractions. The results showed that the lipid in milk can clog the column or adhere to the resin through hydrophobic interaction, leading to an increase in column pressure. Some casein molecules were found to adsorb onto the resin through electrostatic interaction, therefore the adsorption capacity was decreased. There was no direct interaction between lactose and the resin in the chromatorgraphic process. Increased continuous chromatographic cycles and prolonged time interval between protein purification and column regeneration could enhance the undesirable interaction between the contaminants and resin, thus lowering the regeneration efficiency. NaOH was found to be effective in the removal of lipid and casein molecules from the column. Furthermore, normal microstructure and chromatographic performance of the ion exchanger was recovered after this cleaning procedure.
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Role of sexual transmission of HIV among young noninjection and injection opiate users: a respondent-driven sampling study.
Sex Transm Dis
PUBLISHED: 11-16-2011
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Sexual transmissibility of HIV among young drug users in China has been investigated in few studies. The objective of this study was to examine the role of sexual transmission on HIV infection among injection drug users (IDUs) and noninjection drug users (NIDUs).
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