JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Trisulfur Radical Anion as the Key Intermediate for the Synthesis of Thiophene via the Interaction between Elemental Sulfur and NaOtBu.
Org. Lett.
PUBLISHED: 11-20-2014
Show Abstract
Hide Abstract
A facile base-promoted sulfur-centered radical generation mode and a single-step protocol for the synthesis of thiophene derivatives using 1,3-diynes via the interaction between elemental sulfur and NaOtBu has been reported. EPR experiments revealed that the trisulfur radical anion acts as a key intermediate of this process. A plausible mechanism has been proposed.
Related JoVE Video
Enhanced visible light photocatalytic activity of Cu2O via cationic-anionic passivated codoping.
Phys Chem Chem Phys
PUBLISHED: 11-20-2014
Show Abstract
Hide Abstract
To improve the photocatalytic activity of Cu2O for hydrogen production through water splitting, the band edges of Cu2O should be modified to meet the electronic transition of angular momentum selection rules (?l = ±1) and match with the hydrogen or oxygen production levels. Upon analyzing the band structure of Cu2O and the chemical potentials of the dopants, we show that passivated codopants such as (Sn + B) can induce superior modification in the band edges of Cu2O: the conduction band edge is changed from the d band character of Cu atoms to the p band character of the Sn atom and shifted slightly downwards, while the valence band edge keeps the d band character of the Cu atoms and energy unchanged, indicating that the stringent requirements get satisfied. Moreover, the optical absorption spectrum of (Sn + B) codoped Cu2O shows a greatly improved absorption of visible light. The calculated defect formation energy shows that the codoping is energetically more favorable than mono-doping due to the Coulomb interactions and charge compensation effects.
Related JoVE Video
Genital Herpes and Its Treatment in Relation to Preterm Delivery.
Am. J. Epidemiol.
PUBLISHED: 11-12-2014
Show Abstract
Hide Abstract
To examine the risks of genital herpes and antiherpes treatment during pregnancy in relation to preterm delivery (PTD), we conducted a multicenter, member-based cohort study within 4 Kaiser Permanente regions: northern and southern California, Colorado, and Georgia. The study included 662,913 mother-newborn pairs from 1997 to 2010. Pregnant women were classified into 3 groups based on genital herpes diagnosis and treatment: genital herpes without treatment, genital herpes with antiherpes treatment, and no herpes diagnosis or treatment (unexposed controls). After controlling for potential confounders, we found that compared with being unexposed, having untreated genital herpes during first or second trimester was associated with more than double the risk of PTD (odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.80, 2.76). The association was stronger for PTD due to premature rupture of membrane (OR = 3.57, 95% CI: 2.53, 5.06) and for early PTD (?35 weeks gestation) (OR = 2.87, 95% CI: 2.22, 3.71). In contrast, undergoing antiherpes treatment during pregnancy was associated with a lower risk of PTD compared with not being treated, and the PTD risk was similar to that observed in the unexposed controls (OR = 1.11, 95% CI: 0.89, 1.38). The present study revealed increased risk of PTD associated with genital herpes infection if left untreated and a potential benefit of antiherpes medications in mitigating the effect of genital herpes infection on the risk of PTD.
Related JoVE Video
Cu(II)/Cu(I)-Synergistic Cooperation to Lead the Alkyne C-H Activation.
J. Am. Chem. Soc.
PUBLISHED: 11-11-2014
Show Abstract
Hide Abstract
An efficient alkyne C-H activation procedure has been well studied which indicated that a Cu(II)/Cu(I) synergistic co-operation might be involved. In situ Raman spectroscopy was engaged to study kinetic behavior, drawing the conclusion that Cu(II) didn't participate in the rate determining step. IR and X-ray absorption spectroscopy evidence were provided for structural information, indicating that Cu(II) alone couldn't accelerate the reduction procedure by simply coordinating with C-C triple bond to activate the terminal alkynes; meanwhile, X-band EPR spectra and solubility showed that Cu(I) and Cu(II) could affect the complication environment of each other. A distinctive Cu(I)-Cu(II) synergistic cooperation intermediate was proposed for the putative mechanism.
Related JoVE Video
Two novel polymorphisms of bovine SIRT2 gene are associated with higher body weight in Nanyang cattle.
Mol. Biol. Rep.
PUBLISHED: 11-08-2014
Show Abstract
Hide Abstract
Identification of polymorphisms associated with economic traits is important for successful marker-assisted selection in cattle breeding. The family of mammalian sirtuin regulates many biological functions, such as life span extension and energy metabolism. SIRT2, a most abundant sirtuin in adipocytes, acts as a crucial regulator of adipogenic differentiation and plays a key role in controlling adipose tissue function and mass. Here we investigated single nucleotide polymorphisms (SNPs) of bovine SIRT2 in 1226 cattle from five breeds and further evaluated the effects of identified SNPs on economically important traits of Nanyang cattle. Our results revealed four novel SNPs in bovine SIRT2, one was located in intronic region and the other three were synonymous mutations. Linkage disequilibrium and haplotype analyses based on the identified SNPs showed obvious difference between crossbred breed and the other four beef breeds. Association analyses demonstrated that SNPs g.17333C > T and g.17578A > G have a significantly effect on 18-months-old body weight of Nanyang population. Animals with combined genotype TTGG at the above two loci exhibited especially higher body weight. Our data for the first time demonstrated that polymorphisms in bovine SIRT2 are associated with economic traits of Nanyang cattle, which will be helpful for future cattle selection practices.
Related JoVE Video
Arabinoxylan in Wheat is More Responsible Than Cellulose for Promoting the Intestinal Barrier Function in Weaned Male Piglets.
J. Nutr.
PUBLISHED: 11-08-2014
Show Abstract
Hide Abstract
The effect of dietary fiber on intestinal function primarily has been ascribed to its interaction with intestinal bacteria in the hindgut, whereas changes in intestinal bacteria in the host have been considered to depend on fiber composition.
Related JoVE Video
Improved Performance of Colloidal CdSe Quantum Dot-Sensitized Solar Cells by Hybrid Passivation.
ACS Appl Mater Interfaces
PUBLISHED: 11-03-2014
Show Abstract
Hide Abstract
A hybrid passivation strategy is employed to modify the surface of colloidal CdSe quantum dots (QDs) for quantum dot-sensitized solar cells (QDSCs), by using mercaptopropionic acid (MPA) and iodide anions through a ligand exchange reaction in solution. This is found to be an effective way to improve the performance of QDSCs based on colloidal QDs. The results show that MPA can increase the coverage of the QDs on TiO2 electrodes and facilitate the hole extraction from the photoxidized QDs, and simultaneously, that the iodide anions can remedy the surface defects of the CdSe QDs and thus reduce the recombination loss in the device. This hybrid passivation treatment leads to a significant enhancement of the power conversion efficiency of the QDSCs by 41%. Furthermore, an optimal ratio of iodide ions to MPA was determined for favorable hybrid passivation; results show that excessive iodine anions are detrimental to the loading of the QDs. This study demonstrates that the improvement in QDSC performance can be realized by using a combination of different functional ligands to passivate the QDs, and that ligand exchange in solution can be an effective approach to introduce different ligands.
Related JoVE Video
Aggregation Properties of the Small Nuclear Ribonucleoprotein U1-70K in Alzheimer Disease.
J. Biol. Chem.
PUBLISHED: 10-31-2014
Show Abstract
Hide Abstract
Recent evidence indicates that U1-70K and other U1 small nuclear ribonucleoproteins (snRNPs) are sarkosyl-insoluble and associate with tau neurofibrillary tangles selectively in Alzheimer disease (AD). Currently, the mechanisms underlying the conversion of soluble nuclear U1 snRNPs into insoluble cytoplasmic aggregates remain elusive. Based on the biochemical and subcellular distribution properties of U1-70K in AD we hypothesized that aggregated U1-70K itself or other biopolymers (e.g. proteins or nucleic acids) interact with and sequester natively folded soluble U1-70K into insoluble aggregates. Here we demonstrate that total homogenates from AD brain induce soluble U1-70K from control brain or recombinant U1-70K to become sarkosyl-insoluble. This effect was not dependent on RNA, and did not correlate with detergent-insoluble tau levels as AD homogenates with reduced levels of these components were still capable of inducing U1-70K aggregation. In contrast, proteinase K-treated AD homogenates and sarkosyl-soluble AD fractions were unable to induce U1-70K aggregation, indicating that aggregated proteins in AD brain are responsible for inducing soluble U1-70K aggregation. It was determined that the C-terminus of U1-70K, that harbors two disordered low-complexity (LC) domains, is necessary for U1-70K aggregation. Moreover, both LC1 and LC2 domains were sufficient for aggregation. Finally, protein cross-linking and mass spectrometry studies demonstrated that a U1-70K fragment harboring the LC1 domain directly interacts with aggregated U1-70K in AD brain. Our results support a hypothesis that aberrant forms of U1-70K in AD can directly sequester soluble forms of U1-70K into insoluble aggregates.
Related JoVE Video
Podoplanin requires sialylated O-glycans for stable expression on lymphatic endothelial cells and for interaction with platelets.
Blood
PUBLISHED: 10-23-2014
Show Abstract
Hide Abstract
O-glycosylation of podoplanin (PDPN) on lymphatic endothelial cells (LECs) is critical for the separation of blood and lymphatic systems by interacting with platelet C-type lectin-like receptor 2 (CLEC-2) during development. However, how O-glycosylation controls endothelial PDPN function and expression remains unclear. Here we report that core 1 O-glycan-deficient or desialylated PDPN was highly susceptible to proteolytic degradation by various proteases including metalloproteinases MMP-2/9. We found that the lymph contained activated MMP-2/9 and incubation of the lymph reduced surface levels of PDPN on core 1 O-glycan-deficient endothelial cells (ECs), but not on WT ECs. The lymph from mice with sepsis induced by cecal ligation and puncture (CLP), which contained bacteria-derived sialidase, reduced PDPN levels on WT ECs. These reductions were rescued by metalloproteinase inhibitor GM6001. Additionally, GM6001 treatment rescued the reduction of PDPN level on LECs in mice lacking endothelial core 1 O-glycan or CLP-treated mice. Furthermore, core 1 O-glycan-deficient or desialylated PDPN impaired platelet interaction under physiological flow. These data indicate that sialylated O-glycans of PDPN are essential for platelet adhesion and prevent PDPN from proteolytic degradation primarily mediated by metalloproteinases in the lymph.
Related JoVE Video
From hope to hope: The experience of older Chinese people with advanced cancer.
Health (London)
PUBLISHED: 10-22-2014
Show Abstract
Hide Abstract
In our study that explored the current end-of-life care provision for Chinese older people with advanced/terminal cancer, hope emerged as a significant aspect of coping with their condition. Drawing on data from in-depth interviews with a group of older people, their family carers and health professionals, this article explores participants' constructions of hope in terms of what they were hoping for, how their hopes helped them cope with their illness and what sociocultural resources they drew on to build and sustain these hopes. While acknowledging similarities to Western studies of hope in terminal illness, this article identifies significant divergences in terms of the impact of different sociocultural values and their implications for clinical practice in light of an unfavourable health care environment for patients with advanced cancer and a social support system sustained mainly by Chinese families. It argues that hope represents an important resource for coping with terminal illness among these patients.
Related JoVE Video
Observation of valley-dependent beams in photonic graphene.
Opt Express
PUBLISHED: 10-17-2014
Show Abstract
Hide Abstract
Valley-dependent propagation of light in an artificial photonic hexagonal lattice, akin to electrons in graphene, is investigated in microwave regime. Both numerical and experimental results show that the valley degeneracy in the photonic graphene is broken when the frequency is away from the Dirac point. The peculiar anisotropic wave transport property due to distinct valleys is analyzed using the equifrequency contours. More interestingly, the valley-dependent self-collimation and beam splitting phenomena are experimentally demonstrated with the armchair and zigzag interfaces, respectively. Our results confirm that there are two inequivalent Dirac points that lead to two distinct valleys in photonic graphene, which could be used to control the flow of light and might be used to carry information in valley polarized beam splitter, collimator or guiding device.
Related JoVE Video
Temporal and spatial regulation of epsin abundance and VEGFR3 signaling are required for lymphatic valve formation and function.
Sci Signal
PUBLISHED: 10-16-2014
Show Abstract
Hide Abstract
Lymphatic valves prevent the backflow of the lymph fluid and ensure proper lymphatic drainage throughout the body. Local accumulation of lymphatic fluid in tissues, a condition called lymphedema, is common in individuals with malformed lymphatic valves. The vascular endothelial growth factor receptor 3 (VEGFR3) is required for the development of lymphatic vascular system. The abundance of VEGFR3 in collecting lymphatic trunks is high before valve formation and, except at valve regions, decreases after valve formation. We found that in mesenteric lymphatics, the abundance of epsin 1 and 2, which are ubiquitin-binding adaptor proteins involved in endocytosis, was low at early stages of development. After lymphatic valve formation, the initiation of steady shear flow was associated with an increase in the abundance of epsin 1 and 2 in collecting lymphatic trunks, but not in valve regions. Epsin 1 and 2 bound to VEGFR3 and mediated the internalization and degradation of VEGFR3, resulting in termination of VEGFR3 signaling. Mice with lymphatic endothelial cell-specific deficiency of epsin 1 and 2 had dilated lymphatic capillaries, abnormally high VEGFR3 abundance in collecting lymphatics, immature lymphatic valves, and defective lymph drainage. Deletion of a single Vegfr3 allele or pharmacological suppression of VEGFR3 signaling restored normal lymphatic valve development and lymph drainage in epsin-deficient mice. Our findings establish a critical role for epsins in the temporal and spatial regulation of VEGFR3 abundance and signaling in collecting lymphatic trunks during lymphatic valve formation.
Related JoVE Video
[Long-term efficacy of laser peripheral iridotomy in preventing progression in eyes with pigment dispersion syndrome].
Zhonghua Yan Ke Za Zhi
PUBLISHED: 10-15-2014
Show Abstract
Hide Abstract
To evaluate the long-term efficacy of laser peripheral iridotomy (LPI) in preventing deterioration in eyes with pigment dispersion syndrome (PDS).
Related JoVE Video
6-O-Sulfated Chitosan Promoting the Neural Differentiation of Mouse Embryonic Stem Cells.
ACS Appl Mater Interfaces
PUBLISHED: 10-11-2014
Show Abstract
Hide Abstract
Embryonic stem cells (ESCs) can be induced to differentiate into nerve cells, endowing them with potential applications in the treatment of neurological diseases and neural repair. In this work, we report for the first time that sulfated chitosan can promote the neural differentiation of ESCs. As a type of sulfated glycosaminoglycan analog, sulfated chitosan with well-defined sulfation sites and a controlled degree of sulfation (DS) were prepared through simple procedures and the influence of sulfated glycosaminoglycan on neural differentiation of ESCs was investigated. Compared with other sulfation sites, 6-O-sulfated chitosan showed the most optimal effects. By monitoring the expression level of neural differentiation markers using immunofluorescence staining and PCR, it was found that neural differentiation was better enhanced by increasing the DS of 6-O-sulfated chitosan. However, increasing the DS by introducing another sulfation site in addition to the 6-O site to chitosan did not promote neural differentiation as much as 6-O-sulfated chitosan, indicating that compared with DS, the sulfation site is more important. Additionally, the optimal concentration and incubation time of 6-O-sulfated chitosan were investigated. Together, our results indicate that the sulfate site and the molecular structure in a sulfated polysaccharide are very important for inducing the differentiation of ESCs. Our findings may help to highlight the role of sulfated polysaccharide in inducing the neural differentiation of ESCs.
Related JoVE Video
I2-catalyzed oxidative C(sp(3))-H/S-H coupling: utilizing alkanes and mercaptans as the nucleophiles.
Chem. Commun. (Camb.)
PUBLISHED: 10-10-2014
Show Abstract
Hide Abstract
By using alkanes and mercaptans as the nucleophiles with di-tert-butyl peroxide (DTBP) as the oxidant, I2-catalyzed oxidative C(sp(3))-H/S-H coupling was achieved. This protocol provides a novel process to construct C(sp(3))-S bonds from commercially available hydrocarbons and mercaptans.
Related JoVE Video
Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials.
Respir Care
PUBLISHED: 10-02-2014
Show Abstract
Hide Abstract
Randomized trials and meta-analyses have reached conflicting conclusions regarding the risk benefit ratio of thrombolytic therapy or anticoagulant therapy in patients with moderate pulmonary embolism. To investigate the effect of initial thrombolysis and anticoagulant therapy in patients with moderate pulmonary embolism, we performed an updated meta-analysis.
Related JoVE Video
Apigenin inhibits migration and invasion via modulation of epithelial mesenchymal transition in prostate cancer.
Mol Med Rep
PUBLISHED: 10-01-2014
Show Abstract
Hide Abstract
The mortality rate associated with prostate cancer is mainly due to metastases rather than primary organ?confined disease. Decreasing the incidence of metastasis is important in treating prostate cancer. 4',5,7?trihydroxyflavone (apigenin) has been demonstrated to be effective in inhibiting several types of cancer. The aim of this study was to investigate the effect and mechanism of apigenin on the movement of prostate cancer cells. In the present study, DU145 cells were treated with varying concentrations of apigenin for different time periods. Cell viability was evaluated using an MTT assay. Cell motility and invasiveness were assayed using wound healing assays and a Matrigel migration and invasion assay. Flow cytometric and western blot analyses were performed to examine the cell cycle and signaling pathways. The results demonstrated that apigenin suppressed the proliferation and inhibited the migration and invasive potential of the DU145 prostate cancer cells in a dose? and time?dependent manner, which was associated with epithelial mesenchymal transition. These findings suggested that apigenin may be effective in treating human prostate cancer.
Related JoVE Video
ZM-66, a new podophyllotoxin derivative inhibits proliferation and induces apoptosis in K562/ADM cells.
Chin. Med. Sci. J.
PUBLISHED: 09-30-2014
Show Abstract
Hide Abstract
To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM.
Related JoVE Video
Increased Spinal Cord Na+-K+-2Cl- Cotransporter-1 (NKCC1) Activity Contributes to Impairment of Synaptic Inhibition in Paclitaxel-induced Neuropathic Pain.
J. Biol. Chem.
PUBLISHED: 09-24-2014
Show Abstract
Hide Abstract
Microtubule-stabilizing agents, such as paclitaxel (Taxol), are effective chemotherapy drugs for treating many cancers, and painful neuropathy is a major dose-limiting adverse effect. Cation-chloride cotransporters, such as Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) and K(+)-Cl(-) cotransporter-2 (KCC2), critically influence spinal synaptic inhibition by regulating intracellular chloride concentrations. Here we show that paclitaxel treatment in rats significantly reduced GABA-induced membrane hyperpolarization and caused a depolarizing shift in GABA reversal potential of dorsal horn neurons. However, paclitaxel had no significant effect on AMPA or NMDA receptor-mediated glutamatergic input from primary afferents to dorsal horn neurons. Paclitaxel treatment significantly increased protein levels, but not mRNA levels, of NKCC1 in spinal cords. Inhibition of NKCC1 with bumetanide reversed the paclitaxel effect on GABA-mediated hyperpolarization and GABA reversal potentials. Also, intrathecal bumetanide significantly attenuated hyperalgesia and allodynia induced by paclitaxel. Co-immunoprecipitation revealed that NKCC1 interacted with ?-tubulin and ?-actin in spinal cords. Remarkably, paclitaxel increased NKCC1 protein levels at the plasma membrane and reduced NKCC1 levels in the cytosol of spinal cords. In contrast, treatment with an actin-stabilizing agent had no significant effect on NKCC1 protein levels in the plasma membrane or cytosolic fractions of spinal cords. In addition, inhibition of the motor protein dynein blocked paclitaxel-induced subcellular redistribution of NKCC1, whereas inhibition of kinesin-5 mimicked the paclitaxel effect. Our findings suggest that increased NKCC1 activity contributes to diminished spinal synaptic inhibition and neuropathic pain caused by paclitaxel. Paclitaxel disrupts intracellular NKCC1 trafficking by interfering with microtubule dynamics and associated motor proteins.
Related JoVE Video
Deregulation of miR-128 in ovarian cancer promotes cisplatin resistance.
Int. J. Gynecol. Cancer
PUBLISHED: 09-24-2014
Show Abstract
Hide Abstract
Platinum-based chemotherapy is the standard treatment in advanced ovarian cancer, but most patients will relapse with drug-resistant disease. MicroRNAs have been demonstrated to function in chemoresistance in cancers. In this study, we focused on the role of miR-128 in cisplatin-resistant ovarian cancer.
Related JoVE Video
Copper-Catalyzed Radical Carbooxygenation: Alkylation and Alkoxylation of Styrenes.
Chem Asian J
PUBLISHED: 09-19-2014
Show Abstract
Hide Abstract
A simple copper-catalyzed direct radical carbooxygenation of styrenes is developed utilizing alkyl bromides as radical resources. This catalytic radical difunctionalization accomplishes both alkylation and alkoxylation of styrenes in one pot. A broad range of styrenes and alcohols are well tolerated in this transformation. The EPR experiment shows that alkyl halides could oxidize Cu(I) to Cu(II) in this transformation.
Related JoVE Video
[Expression of Annexin A1 in paclitaxel-resistant ovarian carcinoma and its clinical significance].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 09-10-2014
Show Abstract
Hide Abstract
To investigate the correlation of Annexin A1 (ANXA1) expression with paclitaxel response and clinicopathological features of ovarian carcinoma.
Related JoVE Video
BMP2-SMAD signaling represses the proliferation of embryonic neural stem cells through YAP.
J. Neurosci.
PUBLISHED: 09-05-2014
Show Abstract
Hide Abstract
Previous studies have shown that the Hippo pathway effector yes-associated protein (YAP) plays an important role in maintaining stem cell proliferation. However, the precise molecular mechanism of YAP in regulating murine embryonic neural stem cells (NSCs) remains largely unknown. Here, we show that bone morphogenetic protein-2 (BMP2) treatment inhibited the proliferation of mouse embryonic NSCs, that YAP was critical for mouse NSC proliferation, and that BMP2 treatment-induced inhibition of mouse NSC proliferation was abrogated by YAP knockdown, indicating that the YAP protein mediates the inhibitory effect of BMP2 signaling. Additionally, we found that BMP2 treatment reduced YAP nuclear translocation, YAP-TEAD interaction, and YAP-mediated transactivation. BMP2 treatment inhibited YAP/TEAD-mediated Cyclin D1 (ccnd1) expression, and knockdown of ccnd1 abrogated the BMP2-mediated inhibition of mouse NSC proliferation. Mechanistically, we found that Smad1/4, effectors of BMP2 signaling, competed with YAP for the interaction with TAED1 and inhibited YAP's cotranscriptional activity. Our data reveal mechanistic cross talk between BMP2 signaling and the Hippo-YAP pathway in murine NSC proliferation, which may be exploited as a therapeutic target in neurodegenerative diseases and aging.
Related JoVE Video
Layered V-B-O polyoxometalate nets linked by diethylenetriamine complexes with dangling amine groups.
Dalton Trans
PUBLISHED: 09-04-2014
Show Abstract
Hide Abstract
Two layered V-B-O contained polyoxometalate (POM) net structures, denoted as SUT-12 and SUT-13, are reported here. SUT-12 was synthesized by the boric acid flux method, and it represents the first 2D structure constructed from the V6B20 vanadoborate cluster. SUT-13 was synthesized by the hydrothermal method and constructed from V12B6P12 vanadium borophosphate clusters. In both structures, the vanadoborate or vanadium borophosphate clusters were linked through in situ formed Zn(DETA)2 or Cu(DETA)2 complexes. Surprisingly, for all DETA molecules in the two metal complexes, there is one dangling amine group when it is coordinated to the metal. The phenomenon of the dangling amine group feature is abnormal and the Cu(DETA)2 complexes in SUT-13 were taken as an example and studied by the density functional theory (DFT) calculations in order to understand this unusual feature.
Related JoVE Video
Efficient synthesis of 1,2,3-triazoles by copper-mediated c?n and n?n bond formation starting from N-tosylhydrazones and amines.
Chemistry
PUBLISHED: 09-03-2014
Show Abstract
Hide Abstract
An effective copper-mediated synthesis of 1,5-dialkyl-4-aryl-1,2,3-triazoles and 1,4-dialkyl-5-aryl-1,2,3-triazoles has been achieved by the use of different N-tosylhydrazones and alkyl amines. The scope of the substrates could be extended from anilines to aliphatic amines when 30?mol?% amino acid is added into the reaction mixture. This methodology exhibits many notable features, such as broad substrates scope, high efficiency, and good regioselectivity. Preliminary mechanistic studies indicated that the reaction probably proceeded through a 1-tosyl-2-vinyldiazene intermediate and subsequent aza-Michael addition and N?N bond formation process.
Related JoVE Video
C6 ceramide sensitizes pemetrexed-induced apoptosis and cytotoxicity in osteosarcoma cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-22-2014
Show Abstract
Hide Abstract
Chemotherapy has significantly improved the prognosis of high-grade osteosarcoma (OS), but over 30% of OS patients can still not be cured. Pemetrexed, the newly-developed anti-folate chemotherapy drug, exerted lower efficacy against OS cells. Here, we aimed to increase pemetrexed efficiency, and found that the cell-permeable short-chain ceramide (C6) significantly enhanced pemetrexed-induced viability reduction and death in cultured OS cell lines (U2OS and MG-63). Pemetrexed induced moderate apoptosis in OS cells, which was dramatically augmented by C6 ceramide. The apoptosis inhibitor z-VAD-fmk largely inhibited C6 ceramide plus pemetrexed-induced cytotoxicity and apoptosis in OS cells. By using pharmacological and siRNA-knockdown strategies, we showed that Akt-mammalian TOR (mTOR) over-activation was an important pemetrexed resistance factor in OS cells, and C6 ceramide-mediated pemetrexed sensitization effect was mediated, at least in part, by Akt-mTOR inhibition. Finally, we found that Akt-S6 Kinase 1 (S6K1, an indicator of mTOR activation) was over-activated in human OS tissues. On the other hand, the osteoblastic MC3T3-E1 cells, which expressed lower Akt-S6K1 phosphorylation, were resistant to pemetrexed and/or C6 ceramide. Together, we conclude that C6 ceramide sensitizes pemetrexed-induced apoptosis and cytotoxicity in OS cells probably through in-activation of Akt-mTOR signaling.
Related JoVE Video
Maternal vitamin d deficiency and fetal programming - lessons learned from humans and mice.
Kidney Blood Press. Res.
PUBLISHED: 08-19-2014
Show Abstract
Hide Abstract
Cardiovascular disease partially originates from poor environmental and nutritional conditions in early life. Lack of micronutrients like 25 hydroxy vitamin D3 (25OHD) during pregnancy may be an important treatable causal factor. The present study explored the effect of maternal 25OHD deficiency on the offspring.
Related JoVE Video
Attention and recognition biases associated with stature dissatisfaction among young men in China.
Body Image
PUBLISHED: 08-16-2014
Show Abstract
Hide Abstract
This research evaluated information-processing biases related to height dissatisfaction among young Chinese men. In Study 1, 32 highly stature dissatisfied (HSD) men and 36 less stature dissatisfied (LSD) men performed a dot probe task featuring height-related words and neutral words. HSD men were significantly slower than LSD men were in responding to probes that followed short stature words, but the groups did not differ in response speeds to probes that followed tall stature or neutral words. In Study 2, 33 HSD men and 34 LSD men completed an implicit learning task followed by a word recognition task. HSD men recognized significantly more short stature words from the initial task, but recognition accuracy for other word types did not differ between groups. Together, these findings suggest that HSD men are more inclined than LSD men to selectively avoid cues that reflect shortness in stature and to selectively recognize such cues later.
Related JoVE Video
Indium segregation measured in InGaN quantum well layer.
Sci Rep
PUBLISHED: 08-12-2014
Show Abstract
Hide Abstract
The indium segregation in InGaN well layer is confirmed by a nondestructive combined method of experiment and numerical simulation, which is beyond the traditional method. The pre-deposited indium atoms before InGaN well layer growth are first carried out to prevent indium atoms exchange between the subsurface layer and the surface layer, which results from the indium segregation. The uniform spatial distribution of indium content is achieved in each InGaN well layer, as long as indium pre-deposition is sufficient. According to the consistency of the experiment and numerical simulation, the indium content increases from 16% along the growth direction and saturates at 19% in the upper interface, which cannot be determined precisely by the traditional method.
Related JoVE Video
Antibiotic-resistant genes and antibiotic-resistant bacteria in the effluent of urban residential areas, hospitals, and a municipal wastewater treatment plant system.
Environ Sci Pollut Res Int
PUBLISHED: 07-30-2014
Show Abstract
Hide Abstract
In this study, we determined the abundance of 8 antibiotics (3 tetracyclines, 4 sulfonamides, and 1 trimethoprim), 12 antibiotic-resistant genes (10 tet, 2 sul), 4 antibiotic-resistant bacteria (tetracycline, sulfamethoxazole, and combined resistance), and class 1 integron integrase gene (intI1) in the effluent of residential areas, hospitals, and municipal wastewater treatment plant (WWTP) systems. The concentrations of total/individual targets (antibiotics, genes, and bacteria) varied remarkably among different samples, but the hospital samples generally had a lower abundance than the residential area samples. The WWTP demonstrated removal efficiencies of 50.8 % tetracyclines, 66.8 % sulfonamides, 0.5 logs to 2.5 logs tet genes, and less than 1 log of sul and intI1 genes, as well as 0.5 log to 1 log removal for target bacteria. Except for the total tetracycline concentration and the proportion of tetracycline-resistant bacteria (R (2)?=?0.330, P??0.05). In contrast, various relationships were identified between antibiotics and antibiotic resistance genes (P?
Related JoVE Video
Copper-catalysed direct radical alkenylation of alkyl bromides.
Org. Biomol. Chem.
PUBLISHED: 07-29-2014
Show Abstract
Hide Abstract
A copper-catalysed direct radical alkenylation of various benzyl bromides and ?-carbonyl alkyl bromides has been developed. Compared with the recent radical alkenylations which mostly focused on secondary or tertiary alkyl halides, this transformation shows good reactivity to primary alkyl halides and tertiary, secondary alkyl halides were also tolerated. The key initiation step of this transformation is a copper-induced single-electron reduction of C-Br bonds to generate alkyl radical species.
Related JoVE Video
Carbon-centered radical addition to o?c of amides or esters as a route to c?o bond formations.
Chemistry
PUBLISHED: 07-27-2014
Show Abstract
Hide Abstract
Among various types of radical reactions, the addition of carbon radicals to unsaturated bonds is a powerful tool for constructing new chemical bonds, in which the typical applied unsaturated substrates include alkenes, alkynes and imines. Carbonyl is perhaps the most common unsaturated group in nature. This work demonstrates a novel C?O bond formation through carbon-centered radical addition to the carbonyl oxygen of amide or ester, in which amide and ester groups are easily activated through the radical process. EPR spectroscopy and radical clock experiments support the radical process for this transformation, and density functional theory (DFT) calculations support the possibility of carbon-centered radical addition to the carbonyl oxygen of amides or esters.
Related JoVE Video
Adsorption of Fibronectin on Salt-Etched Polyelectrolyte Multilayers and its Roles in Mediating the Adhesion and Migration of Vascular Smooth Muscle Cells.
Macromol Biosci
PUBLISHED: 07-26-2014
Show Abstract
Hide Abstract
Protein adsorption on biomaterials strongly mediates the subsequent cell responses. Here adsorption of fibronectin (Fn) on salt-treated PEI(PSS/PDDA)7 multilayers was characterized. The amounts of adsorbed Fn increased linearly along with the increase of thickness of multilayers pretreated with 1 M and 5 M NaCl solutions (Multilayer-1M and 5M), but was independent on the thickness of Multilayer-3M. The normalized relative RGD activity of Fn were significantly higher on the Multilayer-3M than on others. By comparison of cellular behaviors of VSMCs being cultured in the normal and Fn-depleted serum-containing medium, the significant role of Fn on modulating the behaviors of VSMCs was verified. The Fn adsorption model and its role on linking the biomaterials surface to the VSMCs behaviors are proposed.
Related JoVE Video
SPAK and OSR1 Dependent Down-Regulation of Murine Renal Outer Medullary K Channel ROMK1.
Kidney Blood Press. Res.
PUBLISHED: 07-17-2014
Show Abstract
Hide Abstract
The kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) participate in the regulation of the NaCl cotransporter NCC and the Na(+),K(+),2Cl(-) cotransporter NKCC2. The kinases are regulated by WNK (with-no-K[Lys]) kinases. Mutations of genes encoding WNK kinases underly Gordon's syndrome, a monogenic disease leading to hypertension and hyperkalemia. WNK kinases further regulate the renal outer medullary K(+) channel ROMK1. The present study explored, whether SPAK and/or OSR1 have similarly the potential to modify the activity of ROMK1.
Related JoVE Video
Genome-wide DNA Methylation Profiles and Their Relationships with mRNA and the microRNA Transcriptome in Bovine Muscle Tissue (Bos taurine).
Sci Rep
PUBLISHED: 07-10-2014
Show Abstract
Hide Abstract
DNA methylation is a key epigenetic modification in mammals and plays important roles in muscle development. We sampled longissimus dorsi muscle (LDM) from a well-known elite native breed of Chinese Qinchuan cattle living within the same environment but displaying distinct skeletal muscle at the fetal and adult stages. We generated and provided a genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA for fetal and adult muscle studies. Integration analysis revealed a total of 77 and 1,054 negatively correlated genes with methylation in the promoter and gene body regions, respectively, in both the fetal and adult bovine libraries. Furthermore, we identified expression patterns of high-read genes that exhibit a negative correlation between methylation and expression from nine different tissues at multiple developmental stages of bovine muscle-related tissue or organs. In addition, we validated the MeDIP-Seq results by bisulfite sequencing PCR (BSP) in some of the differentially methylated promoters. Together, these results provide valuable data for future biomedical research and genomic and epigenomic studies of bovine skeletal muscle that may help uncover the molecular basis underlying economically valuable traits in cattle. This comprehensive map also provides a solid basis for exploring the epigenetic mechanisms of muscle growth and development.
Related JoVE Video
3D imaging of transition metals in the zebrafish embryo by X-ray fluorescence microtomography.
Metallomics
PUBLISHED: 07-05-2014
Show Abstract
Hide Abstract
Synchrotron X-ray fluorescence (SXRF) microtomography has emerged as a powerful technique for the 3D visualization of the elemental distribution in biological samples. The mechanical stability, both of the instrument and the specimen, is paramount when acquiring tomographic projection series. By combining the progressive lowering of temperature method (PLT) with femtosecond laser sectioning, we were able to embed, excise, and preserve a zebrafish embryo at 24 hours post fertilization in an X-ray compatible, transparent resin for tomographic elemental imaging. Based on a data set comprised of 60 projections, acquired with a step size of 2 ?m during 100 hours of beam time, we reconstructed the 3D distribution of zinc, iron, and copper using the iterative maximum likelihood expectation maximization (MLEM) reconstruction algorithm. The volumetric elemental maps, which entail over 124 million individual voxels for each transition metal, revealed distinct elemental distributions that could be correlated with characteristic anatomical features at this stage of embryonic development.
Related JoVE Video
Chemical Modification and Energetically Favorable Atomic Disorder of a Layered Thermoelectric Material TmCuTe2 Leading to High Performance.
Chemistry
PUBLISHED: 07-04-2014
Show Abstract
Hide Abstract
Thermoelectric (TE) materials have continuously attracted interest worldwide owing to their capability of converting heat into electricity. However, discovery and design of new TE material system remains one of the greatest difficulties. A TE material, TmCuTe2 , has been designed by a substructure approach and successfully synthesized. The structure mainly features CuTe4 -based layers stacking along the c axis that are separated by Tm(3+) cations. Such an intrinsic Cu site vacancy structure undergoes a first-order phase transition at around 606?K driven by the energetically favorable uniform Cu atom re-distribution on the covalent CuTe4 -based layer substructure, as shown by crystal structure simulations and variable-temperature XRD data. Featured with very low thermal conductivity (ca. 0.6?W?m(-1) ?K(-1) ), large Seebeck coefficient (+185??V?K(-1) ), and moderate electrical conductivity (220?S?cm(-1) ), TmCuTe2 has a maximum ZT of 0.81 at 745?K, which is nine times higher than the value of 0.09 for binary Cu2 Te, thus making it a promising candidate for mid-temperature TE applications. Theoretical studies uncover the electronic structure modifications from the metallic Cu2 Te to the narrow gap semiconductor TmCuTe2 that lead to such a remarkable performance enhancement.
Related JoVE Video
Downregulation of FoxM1 inhibits proliferation, invasion and angiogenesis of HeLa cells in vitro and in vivo.
Int. J. Oncol.
PUBLISHED: 06-30-2014
Show Abstract
Hide Abstract
FoxM1 is a specific transcription factor that has an important function in aggressive human carcinomas, including cervical cancer. However, the specific function and internal molecular mechanism in cervical cancer remain unclear. In this study, RNAi-mediated FoxM1 knockdown inhibited cell growth. This process also decreased the migration and invasion activities of HeLa cells in vitro. Downregulation of FoxM1 inhibited tumor growth and angiogenesis in vivo. In addition, the expressions of uPA, matrix metalloproteinase (MMP)-2, MMP-9 and VEGF were significantly decreased in vitro and in vivo. These results suggested that the inactivation of FoxM1 could be a novel therapeutic target for cervical cancer treatment.
Related JoVE Video
Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-16-2014
Show Abstract
Hide Abstract
Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson disease.
Related JoVE Video
Downregulation of ribosomal protein S6 inhibits the growth of non-small cell lung cancer by inducing cell cycle arrest, rather than apoptosis.
Cancer Lett.
PUBLISHED: 06-07-2014
Show Abstract
Hide Abstract
Ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit, has been found to be associated with multiple physiological and pathophysiological functions. However, its effects and mechanisms in non-small cell lung cancer (NSCLC) still remain unknown. Here, we showed that expressions of total rpS6 and phosphorylation rpS6 (p-rpS6) were both significantly overexpressed in NSCLC. Further survival analysis revealed the shortened overall survival (OS) and relapse-free survival (RFS) in p-rpS6 overexpressed patients and confirmed it as an independent adverse predictor. Stable downregulation of rpS6 in lung adenocarcinoma A549 and squamous cell carcinoma H520 cell lines was then achieved by two specific small hairpin RNA (shRNA) lentiviruses separately. Subsequent experiments showed that downregulation of rpS6 dramatically inhibited cell proliferation in vitro and tumorigenicity in vivo. Moreover, loss of rpS6 promoted cells arrested in G0-G1 phase and reduced in G2-M phase, along with the expression alterations of relative proteins. However, no notable change in apoptosis was observed. Collectively, these results suggested that rpS6 is overactivated in NSCLC and its downregulation suppresses the growth of NSCLC mainly by inducing G0-G1 cell cycle arrest rather than apoptosis.
Related JoVE Video
Copper-catalysed oxidative Csp(3)-H methylenation to terminal olefins using DMF.
Chem. Commun. (Camb.)
PUBLISHED: 06-05-2014
Show Abstract
Hide Abstract
A copper-catalysed direct oxidative Csp(3)-H methylenation to terminal olefins using DMF as one carbon source was developed. In this reaction, various functional groups were well tolerated, thus providing a simple way to construct arylvinylketones and arylvinylpyridines. The preliminary mechanistic investigations revealed that CH2 was from DMF (N-CH3).
Related JoVE Video
Gangliocytomas in the sellar region.
Clin Neurol Neurosurg
PUBLISHED: 05-21-2014
Show Abstract
Hide Abstract
Gangliocytomas occurring in the sellar region are extremely rare. We examined a cohort of these tumors to examine their clinical presentations and prognoses. Between January 2000 and December 2012, 23 patients were diagnosed with sellar region gangliocytomas in Huashan Hospital. These patients were retrospectively reviewed for medical histories, endocrinological examinations, preoperative magnetic resonance imaging (MRI), pathological findings and follow-ups. Endocrinological tests revealed elevated prolactin (PRL) levels in 10 cases (43.5%) and elevated growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in 9 cases (39.1%). Scattered ganglion cells admixed with adenomatous components were observed in 16 cases (69.6%). In the remaining 7 cases (30.4%), only fragments with ganglion cells dispersed in the fibrillar matrix without adenohypophyseal components were detected. Immunohistochemistry revealed PRL-positive adenomas in 6 cases (26.1%) and GH-positive adenomas in 8 cases (34.8%). The average follow-up period was 4.2 years (range: 1-12.7 years). Gross total resection was achieved in 20 cases (87.0%). One patient recurred five years after tumor resection (4.3%). One patient died of acute myocardial infarction six years after operation. Gangliocytomas located in the sellar region may represent a unique immunopathological entity. The surgical results and prognoses of the gangliocytomas were comparable with those of pituitary adenomas.
Related JoVE Video
Chemisorption-induced two- to three-dimensions structural transformations in gold pentamer (CO)nAu 5 (-) (n =0-5).
J Mol Model
PUBLISHED: 05-08-2014
Show Abstract
Hide Abstract
Understanding the geometry structures of gold clusters, especially with adsorbates, is essential for designing highly active gold nanocatalysts. Here, CO chemisorption onto the Au5 (-) cluster is investigated using the density functional calculations. It is found that chemisorption of CO molecules can induce previously unreported two- to three-dimensions (3D) structural changes. Even a single CO chemisorption induces a major structural change to explain the huge blue-shift in photoelectron spectroscopy (PES). The apex site in the parent Au5 (-) cluster is not always the most preferred site for the chemisorption, and two bridged adsorption CO molecules are observed in the lowest-energy (CO)3Au5 (-) cluster. A clear splitting is observed in the first PES of (CO)4Au5 (-), and calculated planar and 3D geometries are likely coexisting in the cluster beam. The fifth CO adsorption leads to the structural transformation of Au5 skeleton to create more apex sites to accommodate five CO molecules. The structural properties, together with the vertical electron detachment energy (VDE) and binding energies calculations indicate that the chemisorption-saturated number is 5.
Related JoVE Video
Design, synthesis and in vitro and in vivo antitumour activity of 3-benzylideneindolin-2-one derivatives, a novel class of small-molecule inhibitors of the MDM2-p53 interaction.
Eur J Med Chem
PUBLISHED: 05-05-2014
Show Abstract
Hide Abstract
A novel class of small-molecule inhibitors of MDM2-p53 interaction with a (E)-3-benzylideneindolin-2-one scaffold was identified using an integrated virtual screening strategy that combined both pharmacophore- and structure-based approaches. The hit optimisation identified several compounds with more potent activity than the hit compound and the positive drug nutlin-3a, especially compound 1b, which exhibited both the highest binding affinity to MDM2 (Ki = 0.093 ?M) and the most potent antiproliferative activity against HCT116 (wild type p53) cells (GI50 = 13.42 ?M). Additionally, 1b dose-dependently inhibited tumour growth in BALB/c mice bearing CT26 colon carcinoma, with no visible sign of toxicity. In summary, compound 1b represents a novel and promising lead structure for the development of anticancer drugs as MDM2-p53 interaction disruptors.
Related JoVE Video
Attention bias in earthquake-exposed survivors: An event-related potential study.
Int J Psychophysiol
PUBLISHED: 04-30-2014
Show Abstract
Hide Abstract
The Chinese Wenchuan earthquake, which happened on the 28th of May in 2008, may leave deep invisible scars in individuals. China has a large number of children and adolescents, who tend to be most vulnerable because they are in an early stage of human development and possible post-traumatic psychological distress may have a life-long consequence. Trauma survivors without post-traumatic stress disorder (PTSD) have received little attention in previous studies, especially in event-related potential (ERP) studies. We compared the attention bias to threat stimuli between the earthquake-exposed group and the control group in a masked version of the dot probe task. The target probe presented at the same space location consistent with earthquake-related words was the congruent trial, while in the space location of neutral words was the incongruent trial. Thirteen earthquake-exposed middle school students without PTSD and 13 matched controls were included in this investigation. The earthquake-exposed group showed significantly faster RTs to congruent trials than to incongruent trials. The earthquake-exposed group produced significantly shorter C1 and P1 latencies and larger C1, P1 and P2 amplitudes than the control group. In particular, enhanced P1 amplitude to threat stimuli was observed in the earthquake-exposed group. These findings are in agreement with the prediction that earthquake-exposed survivors have an attention bias to threat stimuli. The traumatic event had a much greater effect on earthquake-exposed survivors even if they showed no PTSD symptoms than individuals in the controls. These results will provide neurobiological evidences for effective intervention and prevention to post-traumatic mental problems.
Related JoVE Video
Structural analysis of respiratory syncytial virus reveals the position of M2-1 between the matrix protein and the ribonucleoprotein complex.
J. Virol.
PUBLISHED: 04-23-2014
Show Abstract
Hide Abstract
Respiratory syncytial virus (RSV), a member of the Paramyxoviridae family of nonsegmented, negative-sense, single-stranded RNA genome viruses, is a leading cause of lower respiratory tract infections in infants, young children, and the elderly or immunocompromised. There are many open questions regarding the processes that regulate human RSV (hRSV) assembly and budding. Here, using cryo-electron tomography, we identified virus particles that were spherical, filamentous, and asymmetric in structure, all within the same virus preparation. The three particle morphologies maintained a similar organization of the surface glycoproteins, matrix protein (M), M2-1, and the ribonucleoprotein (RNP). RNP filaments were traced in three dimensions (3D), and their total length was calculated. The measurements revealed the inclusion of multiple full-length genome copies per particle. RNP was associated with the membrane whenever the M layer was present. The amount of M coverage ranged from 24% to 86% in the different morphologies. Using fluorescence light microscopy (fLM), direct stochastic optical reconstruction microscopy (dSTORM), and a proximity ligation assay (PLA), we provide evidence illustrating that M2-1 is located between RNP and M in isolated viral particles. In addition, regular spacing of the M2-1 densities was resolved when hRSV viruses were imaged using Zernike phase contrast (ZPC) cryo-electron tomography. Our studies provide a more complete characterization of the hRSV virion structure and substantiation that M and M2-1 regulate virus organization.
Related JoVE Video
Multiphoton microscopy as a diagnostic imaging modality for pancreatic neoplasms without hematoxylin and eosin stains.
J Biomed Opt
PUBLISHED: 04-20-2014
Show Abstract
Hide Abstract
Hematoxylin and eosin (H&E) staining of tissue samples is the standard approach in histopathology for imaging and diagnosing cancer. Recent reports have shown that multiphoton microscopy (MPM) provides better sample interface with single-cell resolution, which enhances traditional H&E staining and offers a powerful diagnostic tool with potential applications in oncology. The purpose of this study was to further expand the versatility of MPM by establishing the optical parameters required for imaging unstained histological sections of pancreatic neoplasms, thereby providing an efficient and environmentally sustainable alternative to H&E staining while improving the accuracy of pancreatic cancer diagnoses. We found that the high-resolution MPM images clearly distinguish between the structure of normal pancreatic tissues compared with pancreatic neoplasms in unstained histological sections, and discernable differences in tissue architecture and cell morphology between normal versus tumorigenic cells led to enhanced optical diagnosis of cancerous tissue. Moreover, quantitative assessment of the cytomorphological features visualized from MPM images showed significant differences in the nuclear–cytoplasmic ratios of pancreatic neoplasms compared with normal pancreas, as well as further distinguished pancreatic malignant tumors from benign tumors. These results indicate that the MPM could potentially serve as an optical tool for the diagnosis of pancreatic neoplasms in unstained histological sections.
Related JoVE Video
Immunoglobulin molecules detection with nanopore sensors fabricated from glass tubes.
J Nanosci Nanotechnol
PUBLISHED: 04-18-2014
Show Abstract
Hide Abstract
Nanopores are increasingly utilized as tools for single molecule detection in biotechnology. Here, we report an improved fabrication process to make solid-state nanopores from glass tubes with the help of paraffin. Based on the physical footprint of the phase change of the paraffin, nanocavity is formed in the broken terminal after thermally compressing and pulling the glass capillary. Nanopores with the minimum diameter of 50 nm are fabricated. Different immunoglobulin molecules including IgG, IgA, IgM mixed in a 10 mM KCl solution are used to test the sensing capabilities of the glass-nanopore sensor. Various modulated ionic current modes were observed while the the three type immunoglobulin molecules translocate the nanopore because the molecules had different size and structure. Based on the difference in the duration time and amplitude of the transient electrical pulse signals, we are able to discriminate the three immunoglobulin molecules.
Related JoVE Video
Clinical characteristics and current management of hepatitis B and C in China.
World J. Gastroenterol.
PUBLISHED: 03-24-2014
Show Abstract
Hide Abstract
To describe a population of outpatients in China infected by hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and assess their current management status.
Related JoVE Video
Engineered insulin secretion from neuroendocrine cells isolated from human thyroid.
World J Surg
PUBLISHED: 02-20-2014
Show Abstract
Hide Abstract
Insulin-secreting beta-like cells are vulnerable to diabetic autoimmunity. We hypothesized that human thyroid neuroendocrine (NE) cells could be engineered to secrete human insulin, be glucose-responsive, and avoid autoimmunity.
Related JoVE Video
Balance between metallothionein and metal response element binding transcription factor 1 is mediated by zinc ions (Review).
Mol Med Rep
PUBLISHED: 02-14-2014
Show Abstract
Hide Abstract
Metal ion homeostasis and heavy metal detoxification systems are regulated by certain genes associated with metal ion transport. Metallothionein (MT) and metal response element binding transcription factor 1 (MTF?1) are important regulatory proteins involved in the mediation of intracellular metal ion balance. Differences in the zinc?binding affinities of the zinc fingers of MTF?1 and the ?? and ??domains of MT facilitate their regulation of Zn2+ concentration. Alterations in the intracellular concentration of Zn2+ influence the MTF?1 zinc finger number, and MTF?1 containing certain zinc finger numbers regulates the expression of corresponding target genes. The present review evaluates the association between zinc finger number in MTF?1 protein, MTF?1 target genes and the mechanism underlying MT regulation of the zinc finger number in MTF?1.
Related JoVE Video
Aggregates of small nuclear ribonucleic acids (snRNAs) in Alzheimer's disease.
Brain Pathol.
PUBLISHED: 02-13-2014
Show Abstract
Hide Abstract
We recently discovered that protein components of the ribonucleic acid (RNA) spliceosome form cytoplasmic aggregates in Alzheimer's disease (AD) brain, resulting in widespread changes in RNA splicing. However, the involvement of small nuclear RNAs (snRNAs), also key components of the spliceosome complex, in the pathology of AD remains unknown. Using immunohistochemical staining of post-mortem human brain and spinal cord, we identified cytoplasmic tangle-shaped aggregates of snRNA in both sporadic and familial AD cases but not in aged controls or other neurodegenerative disorders. Immunofluorescence using antibodies reactive with the 2,2,7-trimethylguanosine cap of snRNAs and transmission electron microscopy demonstrated snRNA localization with tau and paired helical filaments, the main component of neurofibrillary tangles. Quantitative real-time polymerase chain reaction (PCR) showed U1 snRNA accumulation in the insoluble fraction of AD brains whereas other U snRNAs were not enriched. In combination with our previous results, these findings demonstrate that aggregates of U1 snRNA and U1 small nuclear ribonucleoproteins represent a new pathological hallmark of AD.
Related JoVE Video
Imaging the condensation and evaporation of molecularly thin ethanol films with surface forces apparatus.
Rev Sci Instrum
PUBLISHED: 02-13-2014
Show Abstract
Hide Abstract
A new method for imaging condensation and evaporation of molecularly thin ethanol films is reported. It is found that the first adsorbed layer of ethanol film on mica surface behaves as solid like structure that cannot flow freely. With the increase of exposure time, more ethanol molecules condense over the mica surface in the saturated ethanol vapor condition. The first layer of adsorbed ethanol film is about 3.8 Å thick measured from the surface forces apparatus, which is believed to be the average diameter of ethanol molecules while they are confined in between two atomically smooth mica surfaces.
Related JoVE Video
Optical diagnosis of gallbladder cancers via two-photon excited fluorescence imaging of unstained histological sections.
Lasers Med Sci
PUBLISHED: 02-09-2014
Show Abstract
Hide Abstract
Two-photon excited fluorescence (TPEF) microscopy, based on signal from cells, can provide detailed information on tissue architecture and cellular morphology in unstained histological sections to generate subcellular-resolution images from tissue directly. In this paper, we used TPEF microscopy to image microstructure of human normal gallbladder and three types of differentiated carcinomas in order to investigate the morphological changes of tissue structure, cell, cytoplasm, and nucleus without hematoxylin and eosin (H&E) staining. It displayed that TPEF microscopy can well image the stratified normal gallbladder tissue, including the mucosa, the muscularis, and the serosa. The typical cancer cell, characterized by cellular and nuclear pleomorphism, enlarged nuclei, and augmented nucleolus, can be identified in histological sections without H-E staining as well. The quantitative results showed that the areas of the nucleus and the nucleolus in three types of cancerous cells were all significantly greater than those in normal gallbladder columnar epithelial cells derived from TPEF microscopic images. The studies demonstrated that TPEF microscopy has the ability to characterize tissue structures and cell morphology of gallbladder cancers differentiated from a normal gallbladder in a manner similar to traditional histological analysis. As a novel tool, it has the potential for future retrospective studies of tumor staging and migration by utilizing histological section specimens without H-E staining.
Related JoVE Video
U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer's disease due to autosomal dominant genetic mutations and trisomy 21.
Mol Neurodegener
PUBLISHED: 01-31-2014
Show Abstract
Hide Abstract
We recently identified U1 small nuclear ribonucleoprotein (snRNP) tangle-like aggregates and RNA splicing abnormalities in sporadic Alzheimer's disease (AD). However little is known about snRNP biology in early onset AD due to autosomal dominant genetic mutations or trisomy 21 in Down syndrome. Therefore we investigated snRNP biochemical and pathologic features in these disorders.
Related JoVE Video
CD4 T cells require ICOS-mediated PI3K signaling to increase T-Bet expression in the setting of anti-CTLA-4 therapy.
Cancer Immunol Res
PUBLISHED: 01-24-2014
Show Abstract
Hide Abstract
The transcription factor T-bet controls the Th1 genetic program in T cells for effective antitumor responses. Anti-CTLA-4 immunotherapy elicits dramatic antitumor responses in mice and in human patients; however, factors that regulate T-bet expression during an antitumor response mediated by anti-CTLA-4 remain to be elucidated. We were the first to report that treatment with anti-CTLA-4 led to an increase in the frequency of T cells expressing inducible costimulator (ICOS). In both treated patients and mice, our data revealed that CD4(+)ICOS(hi) T cells can act as effector T cells, which produce the Th1 cytokine IFN-?. We also showed in a small retrospective analysis that an increased frequency of CD4(+)ICOS(hi) T cells correlated with better clinical outcome and the absence of ICOS or its ligand (ICOSL) in mouse models led to impaired tumor rejection. Here, we show that CD4(+)ICOS(hi) T cells from anti-CTLA-4-treated patients had an increase in signaling via the phospoinositide-3-kinase (PI3K) pathway and an increase in expression of T-bet. An ICOS-specific siRNA transfected into human T cells led to diminished PI3K signaling and T-bet expression. Therefore, we hypothesized that ICOS, and specifically ICOS-mediated PI3K signaling, was required for T-bet expression. We conducted studies in ICOS-deficient and ICOS-YF mice, which have a single amino acid change that abrogates PI3K signaling by ICOS. We found that ICOS-mediated PI3K signaling is required for T-bet expression during an antitumor response elicited by anti-CTLA-4 therapy. Our data provide new insight into the regulation of T-bet expression and suggest that ICOS can be targeted to improve Th1 antitumor responses.
Related JoVE Video
Synthesis of 6-acyl phenanthridines by oxidative radical decarboxylation-cyclization of ?-oxocarboxylates and isocyanides.
Chem. Commun. (Camb.)
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
A silver catalysed synthesis of 6-acyl phenanthridines by oxidative radical decarboxylation-cyclization of ?-oxocarboxylates and isocyanides was developed. This reaction provided a novel method to realize C1 insertion via a radical process and various functional groups were well-tolerated.
Related JoVE Video
Direct observation of reduction of Cu(II) to Cu(I) by terminal alkynes.
J. Am. Chem. Soc.
PUBLISHED: 01-10-2014
Show Abstract
Hide Abstract
X-ray absorption spectroscopy and in situ electron paramagnetic resonance evidence were provided for the reduction of Cu(II) to Cu(I) species by alkynes in the presence of tetramethylethylenediamine (TMEDA), in which TMEDA plays dual roles as both ligand and base. The structures of the starting Cu(II) species and the obtained Cu(I) species were determined as (TMEDA)CuCl2 and [(TMEDA)CuCl]2 dimer, respectively.
Related JoVE Video
Synthesis and broad-spectrum antiviral activity of some novel benzo-heterocyclic amine compounds.
Molecules
PUBLISHED: 01-08-2014
Show Abstract
Hide Abstract
A series of novel unsaturated five-membered benzo-heterocyclic amine derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that most of our synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compounds 3f (IC50=3.21-5.06 ?M) and 3g (IC50=0.71-34.87 ?M) showed potent activity towards both RNA viruses (influenza A, HCV and Cox B3 virus) and a DNA virus (HBV) at low micromolar concentrations. An SAR study showed that electron-withdrawing substituents located on the aromatic or heteroaromatic ring favored antiviral activity towards RNA viruses.
Related JoVE Video
Myocardial Injury after Surgery Is a Risk Factor for Weaning Failure from Mechanical Ventilation in Critical Patients Undergoing Major Abdominal Surgery.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Myocardial injury after noncardiac surgery (MINS) is a newly proposed concept that is common among adults undergoing noncardiac surgery and associated with substantial mortality. We analyzed whether MINS was a risk factor for weaning failure in critical patients who underwent major abdominal surgery.
Related JoVE Video
Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund's adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-? spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.
Related JoVE Video
Contrasting regeneration strategies in climax and long-lived pioneer tree species in a subtropical forest.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
1: This study investigated 15 coexisting dominant species in a humid subtropical evergreen broad-leaved forest in southwest China, consisting of long-lived pioneers and climax species occurring in natural and disturbed regimes. The authors hypothesized that there would be non-tradeoff scaling relationships between sprouting and seed size among species, with the aim of uncovering the ecological relationship between plant sprouting and seed characteristics in the two functional groups. 2: The sprouting variations of the species were initially examined using pairwise comparisons between natural and disturbed habitats within and across species and were noted to show a continuum in persistence niches across the forest dominants, which may underlie the maintenance of plant diversity. Second, a significantly positive, rather than tradeoff, relationship between sprout number and seed size across species within each of the two functional groups was observed, and an obvious elevational shift with a common slope among the two groups in their natural habitat was examined. The results indicate the following: 1) the relationship of seed size vs. sprouts in the natural habitat is more likely to be bet-hedging among species within a guild in a forest; 2) climax species tend to choose seeding rather than sprouting regeneration, and vice versa for the long-lived pioneers; and 3) the negative correlation between sprouting and seed dispersal under disturbed conditions may imply a tradeoff between dispersal and persistence in situ during the process of plant regeneration. 3: These findings may be of potential significance for urban greening using native species.
Related JoVE Video
Repetitive Transcranial Magnetic Stimulation Promotes Neural Stem Cell Proliferation via the Regulation of MiR-25 in a Rat Model of Focal Cerebral Ischemia.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Repetitive transcranial magnetic stimulation (rTMS) has increasingly been studied over the past decade to determine whether it has a therapeutic benefit on focal cerebral ischemia. However, the underlying mechanism of rTMS in this process remains unclear. In the current study, we investigated the effects of rTMS on the proliferation of adult neural stem cells (NSCs) and explored microRNAs (miRNAs) that were affected by rTMS. Our data showed that 10 Hz rTMS significantly increased the proliferation of adult NSCs after focal cerebral ischemia in the subventricular zone (SVZ), and the expression of miR-25 was obviously up-regulated in the ischemic cortex after rTMS. p57, an identified miR-25 target gene that regulates factors linked to NSC proliferation, was also evaluated, and it exhibited down-regulation. To further verify the role of miR-25, rats were injected with a single dose of antagomir-25 and were subjected to focal cerebral ischemia followed by rTMS treatment. The results confirmed that miR-25 could be repressed specifically and could drive the up-regulation of its target gene (p57), which resulted in the inhibition of adult NSC proliferation in the SVZ after rTMS. Thus, our studies strongly indicated that 10 Hz rTMS can promote the proliferation of adult NSCs in the SVZ after focal cerebral ischemia by regulating the miR-25/p57 pathway.
Related JoVE Video
A new brain drug delivery strategy: focused ultrasound-enhanced intranasal drug delivery.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases.
Related JoVE Video
Increased Expression of Phosphorylated FADD in Anaplastic Large Cell and Other T-Cell Lymphomas.
Biomark Insights
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
FAS-associated protein with death domain (FADD) is a major adaptor protein involved in extrinsic apoptosis, embryogenesis, and lymphocyte homeostasis. Although abnormalities of the FADD/death receptor apoptotic pathways have been established in tumorigenesis, fewer studies have analyzed the expression and role of phosphorylated FADD (pFADD). Our identification of FADD as a lymphoma-associated autoantigen in T-cell lymphoma patients raises the possibility that pFADD, with its correlation with cell cycle, may possess role(s) in human T-cell lymphoma development. This immunohistochemical study investigated pFADD protein expression in a range of normal tissues and lymphomas, particularly T-cell lymphomas that require improved therapies. Whereas pFADD was expressed only in scattered normal T cells, it was detected at high levels in T-cell lymphomas (eg, 84% anaplastic large cell lymphoma and 65% peripheral T cell lymphomas, not otherwise specified). The increased expression of pFADD supports further study of its clinical relevance and role in lymphomagenesis, highlighting phosphorylation of FADD as a potential therapeutic target.
Related JoVE Video
Integrated analysis of differential miRNA and mRNA expression profiles in human radioresistant and radiosensitive nasopharyngeal carcinoma cells.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The purpose of this study was to identify miRNAs and genes involved in nasopharyngeal carcinoma (NPC) radioresistance, and explore the underlying mechanisms in the development of radioresistance.
Related JoVE Video
The M2 polarization of macrophage induced by fractalkine in the endometriotic milieu enhances invasiveness of endometrial stromal cells.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Fractalkine (FKN) is involved in the immunopathogenesis of inflammatory diseases, including endometriosis. Our objective was to investigate the role of FKN in the cross-talking between endometrial stromal cells (ESCs) and U937 (macrophage line) in the endometriotic milieu. We have found that FKN levels in peritoneal fluid and ESCs positively correlate with the progress of endometriosis. The expression of CX3CR1 in the normal ESCs were significantly lower than that in eutopic and ectopic ESCs from women with endometriosis. CX3CR1 expression in U937 was higher than that in ectopic ESCs. FKN secreted by eutopic ESCs could change the balance between the release of IL10 and IL12 of macrophages with the upregulation of IL10 production and downregulation of IL12 production. Moreover, FKN could induce M2 polarization of macrophage with decreased expression of CD86. FKN could increase the expression of matrix metalloproteinase 9 and decrease the expression of tissue inhibitor of metalloproteinase1 and 2, and promote the invasiveness of ESCs by activating p38MAPK and integrin?1 signal pathway. In conclusion, the higher levels of FKN secreted by eutopic ESCs facilitate the onset and progression of endometriosis by inducing M2 polarization of macrophage which in turn enhances invasiveness of ESCs.
Related JoVE Video
[Activation of NOD2 Signalling Pathway Stimulates the Function of Human Dendritic Cells Loaded with Leukemia Cell Lysates].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 12-28-2013
Show Abstract
Hide Abstract
The purpose of this study was to explore the effect of NOD2 signalling pathway activated by muramyl dipeptide (MDP) on the immunomodulation effect of human monocyte-derived dendritic cells (DC) loaded with leukemia cell lysates. Peripheral blood mononuclear cells (PBMNC) were isolated by density gradient centrifugation, These cells were cultured with three cytokines for 7 days to induce their maturation. On the 5th day, cells were loaded with leukemia cell HL-60 lysates. NOD2 expression was detected by RT-PCR and Western blot. The phenotype of DC were analyzed by flow cytometry, and ELISA was used to assay levels of IL-12 (p40) . The results showed that MDP could trigger NOD2 mRNA and protein expression in different groups of DC, especially in sensitized DC+MDP group, which was significantly higher than that in the DC+MDP group and sensitized DC without MDP stimulation, the difference was statistically significant (P < 0.05). Besides, the expression of surface molecules(HLA-DR, CD80, CD83, CD86, CD40) in the group of DC loaded with leukemia cell lysate and stimulated by MDP (sensitized DC+MDP) reached the highest level, followed by the group of DC loaded with leukemia cell lysate without MDP and DC only stimulated by MDP, non-treated DC were the lowest(P < 0.05). Similarly, compared with untreated unstimulated DC, after loading with HL-60 lysates or only stimulating with MDP, the secretion of IL-12p40 increased, but IL-12p40 level (573.86 ± 32.09 pg/ml) in DC+MDP group was higher than that in group of sensitized DC (365.03 ± 28.86 pg/ml) (P < 0.05), and it in sensitized DC+MDP group reached the highest(898.30 ± 61.08) pg/ml, compared to other groups(P < 0.05). It is concluded that MDP can significantly enhance the NOD2 mRNA and protein expression in sensitized DC, promote the expression of HLA-DR, synergistic costimulatory molecules and adhesion molecules of DC, at the same time, MDP can increase secretion of inflammatory factors IL-12p40. This study will provide a new ideas for DC application in leukemia immunotherapy.
Related JoVE Video
Combining Single RNA Sensitive Probes with Subdiffraction-Limited and Live-Cell Imaging Enables the Characterization of Virus Dynamics in Cells.
ACS Nano
PUBLISHED: 12-23-2013
Show Abstract
Hide Abstract
The creation of fluorescently labeled viruses is currently limited by the length of imaging observation time (e.g., labeling an envelope protein) and the rescue of viral infectivity (e.g., encoding a GFP protein). Using single molecule sensitive RNA hybridization probes delivered to the cytoplasm of infected cells, we were able to isolate individual, infectious, fluorescently labeled human respiratory syncytial virus virions. This was achieved without affecting viral mRNA expression, viral protein expression, or infectivity. Measurements included the characterization of viral proteins and genomic RNA in a single virion using dSTORM, the development of a GFP fusion assay, and the development of a pulse-chase assay for viral RNA production that allowed for the detection of both initial viral RNA and nascent RNA production at designated times postinfection. Live-cell measurements included imaging and characterization of filamentous virion fusion and the quantification of virus replication within the same cell over an eight-hour period. Using probe-labeled viruses, individual viral particles can be characterized at subdiffraction-limited resolution, and viral infections can be quantified in single cells over an entire cycle of replication. The implication of this development is that MTRIP labeling of viral RNA during virus assembly has the potential to become a general methodology for the labeling and study of many important RNA viruses.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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