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Find video protocols related to scientific articles indexed in Pubmed.
Multicomponent Reactions of Phosphines, Diynedioates, and Aryl Aldehydes Generated Furans Appending Reactive Phosphorus Ylides through Cumulated Trienoates as Key Intermediates: A Phosphine ?-Addition-?-Evolvement of an Anion Pathway.
Org. Lett.
PUBLISHED: 10-22-2014
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Multicomponent reactions of phosphines, diynedioates, and aryl aldehydes have been demonstrated, providing trisubstituted furans appending reactive phosphorus ylides, through cumulated trienoates as key intermediates. The proposed trienoate intermediates, 1,5-dipolar species formed via nucleophilic ?-attack of phosphines toward diynedioates (?-addition-?-evolvement of an anion, abbreviated ?A?E), undergo addition to aryl aldehydes followed by 5-endo-dig cyclization, proton transfer, and resonance to give trisubstituted furans. Furthermore, the phosphorus ylides are oxidized to ?-keto ester furans and utilized as Wittig reagents.
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Tunable electrofluorochromic device from electrochemically controlled complementary fluorescent conjugated polymer films.
ACS Appl Mater Interfaces
PUBLISHED: 10-03-2014
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The fluorescent behavior of the electrofluorochromic devices (Type I) of greenish-yellow emitting P1 and blue emitting P2 can be reversibly switched between the nonfluorescent (oxidized) state and the fluorescent (neutral) state with a superb on/off ratio of 23.8 and 21.9, respectively. Moreover, a tunable electrofluorochromic device (Type II) based on two P1 and P2 polymeric layers that are coated individually on two independent ITO electrodes shows switchable blue-white-(greenish-yellow) multifluorescence states.
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Chirality control of quadruple helixes of metal strings by peripheral chiral ligands.
Chem Asian J
PUBLISHED: 08-21-2014
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Chirality control of helixes with the ? (P) or ? (M) form is interesting in various fields such as extended metal atom chains (EMACs), in which the metal backbones are helically wrapped by four ligands. Herein, we report two EMACs, ?-[Ni5 ((-)camnpda)4 ] and ?-[Ni5 ((+)camnpda)4 ], whose chiralities are controlled by chiral ligands with naphthyridine and camphorsulfonyl groups. There is a large energy difference (108?kcal?mol(-1) ) between the two helical structures with one chiral ligand. Furthermore, the electron communication between [Ni2 ](3+) units is more pronounced than in [Ni5 (bna)4 Cl2 ](2+) (bna=binaphthyridylamido). The results demonstrate control of small-scale helical structure and set the stage for future development of chiral controlled base and nanoelectronic devices.
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Closely related NDM-1-encoding plasmids from Escherichia coli and Klebsiella pneumoniae in Taiwan.
PLoS ONE
PUBLISHED: 08-21-2014
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Two plasmids carrying blaNDM-1 isolated from carbapenem-resistant Klebsiella pneumoniae (CR-KP) and carbapenem-resistant Escherichia coli (CR-EC) were sequenced. CR-KP and CR-EC were isolated from two Taiwanese patients without travel histories.
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CHRNA9 polymorphisms and smoking exposure synergize to increase the risk of breast cancer in Taiwan.
Carcinogenesis
PUBLISHED: 08-20-2014
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Previous studies indicated that smoking exposure is associated with an increased risk of breast cancer, and ?9-nicotine acetylcholine receptors (?9-nAChRs) are involved in breast tumorigenesis. However, no studies have explored the joint effect of ?9-nAChRs (CHRNA9) genes and cigarette smoking exposure on breast cancer risk. A case-control study was conducted on 737 breast cancer patients and 719 age-matched healthy controls. Three single-nucleotide polymorphisms (SNPs) of CHRNA9 located in the promoter region were genotyped and compared between cases and controls to identify those SNPs associated with breast cancer susceptibility. A dual-luciferase reporter assay was used to analyze the promoter activities of these SNPs of the CHRNA9 gene. After a Bonferroni correction, the G allele of the CHRNA9 rs7329797 SNP was significantly associated with an increased risk of developing breast cancer compared with A/A genotype carriers (odds ratio, 1.8; 95% confidence interval, 1.2-2.6). A multiplicative interaction between passive smoking exposure and the CHRNA9 rs73229797 SNP on the risk of breast malignancy was observed. A functional assay further showed that rs73229797 was associated with increased promoter activity of the CHRNA9 gene. Our findings support a significant interaction effect existing between the CHRNA9 gene and smoking exposure on the risk of breast cancer development.
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The p53-reactivating small molecule RITA induces senescence in head and neck cancer cells.
PLoS ONE
PUBLISHED: 08-13-2014
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TP53 is the most commonly mutated gene in head and neck cancer (HNSCC), with mutations being associated with resistance to conventional therapy. Restoring normal p53 function has previously been investigated via the use of RITA (reactivation of p53 and induction of tumor cell apoptosis), a small molecule that induces a conformational change in p53, leading to activation of its downstream targets. In the current study we found that RITA indeed exerts significant effects in HNSCC cells. However, in this model, we found that a significant outcome of RITA treatment was accelerated senescence. RITA-induced senescence in a variety of p53 backgrounds, including p53 null cells. Also, inhibition of p53 expression did not appear to significantly inhibit RITA-induced senescence. Thus, this phenomenon appears to be partially p53-independent. Additionally, RITA-induced senescence appears to be partially mediated by activation of the DNA damage response and SIRT1 (Silent information regulator T1) inhibition, with a synergistic effect seen by combining either ionizing radiation or SIRT1 inhibition with RITA treatment. These data point toward a novel mechanism of RITA function as well as hint to its possible therapeutic benefit in HNSCC.
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Carbapenems and piperacillin/tazobactam for the treatment of bacteremia caused by extended-spectrum ?-lactamase-producing Proteus mirabilis.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 07-26-2014
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This study was intended to delineate the role of carbapenems and piperacillin/tazobactam in treating bacteremia caused by extended-spectrum ?-lactamase (ESBL)-producing Proteus mirabilis. We performed a multicenter and retrospective study of the patients with ESBL-producing P. mirabilis bacteremia. The outcomes of the patients treated by piperacillin/tazobactam or a carbapenem for at least 48 hours and the MICs of the prescribed drugs for these isolates were analyzed. Forty-seven patients with available clinical data were included. The overall 30-day mortality rate was 29.8%. All available isolates (n = 44) were susceptible to ertapenem, meropenem, and doripenem, and 95.6% were susceptible to piperacillin/tazobactam; however, only 11.4% of the isolates were susceptible to imipenem. Among the 3 patients infected with isolates exhibiting non-susceptibility to imipenem (MIC ?2 mg/L) who were treated with imipenem, none died within 28 days. The 30-day (14.3% versus 23.1%, P = 0.65) or in-hospital (19.1% versus 30.8%, P = 0.68) mortality rate of 21 patients treated by a carbapenem was lower than that of 13 treated by piperacillin/tazobactam. However, among those treated by piperacillin/tazobactam, the mortality rate of those infected by the isolates with lower piperacillin/tazobactam MICs (?0.5/4 mg/L) was lower than that of the isolates with MICs of ?1/4 mg/L (0%, 0/7 versus 60%, 3/5; P = 0.045). ESBL-producing P. mirabilis bacteremia is associated with significant mortality, and carbapenem therapy could be regarded as the drugs of choice. The role of piperacillin/tazobactam, especially for the infections due to the isolates with an MIC ?0.5/4 mg/L, warrants more clinical studies.
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Cell type-dependent RNA recombination frequency in the Japanese encephalitis virus.
Biomed Res Int
PUBLISHED: 07-22-2014
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Japanese encephalitis virus (JEV) is one of approximately 70 flaviviruses, frequently causing symptoms involving the central nervous system. Mutations of its genomic RNA frequently occur during viral replication, which is believed to be a force contributing to viral evolution. Nevertheless, accumulating evidences show that some JEV strains may have actually arisen from RNA recombination between genetically different populations of the virus. We have demonstrated that RNA recombination in JEV occurs unequally in different cell types. In the present study, viral RNA fragments transfected into as well as viral RNAs synthesized in mosquito cells were shown not to be stable, especially in the early phase of infection possibly via cleavage by exoribonuclease. Such cleaved small RNA fragments may be further degraded through an RNA interference pathway triggered by viral double-stranded RNA during replication in mosquito cells, resulting in a lower frequency of RNA recombination in mosquito cells compared to that which occurs in mammalian cells. In fact, adjustment of viral RNA to an appropriately lower level in mosquito cells prevents overgrowth of the virus and is beneficial for cells to survive the infection. Our findings may also account for the slower evolution of arboviruses as reported previously.
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Short-term glutamine supplementation decreases lung inflammation and the receptor for advanced glycation end-products expression in direct acute lung injury in mice.
BMC Pulm Med
PUBLISHED: 07-10-2014
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Glutamine (GLN) has been reported to improve clinical and experimental sepsis outcomes. However, the mechanisms underlying the actions of GLN remain unclear, and may depend upon the route of GLN administration and the model of acute lung injury (ALI) used. The aim of this study was to investigate whether short-term GLN supplementation had an ameliorative effect on the inflammation induced by direct acid and lipopolysaccharide (LPS) challenge in mice.
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Gender-related effects of prefrontal cortex connectivity: a resting-state functional optical tomography study.
Biomed Opt Express
PUBLISHED: 07-07-2014
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The prefrontal cortex (PFC) is thought to play an important role in "higher" brain functions such as personality and emotion that may associated with several gender-related mental disorders. In this study, the gender effects of functional connectivity, cortical lateralization and significantly differences in the PFC were investigated by using resting-state functional optical tomography (fOT) measurement. A total of forty subjects including twenty healthy male and twenty healthy female adults were recruited for this study. In the results, the hemoglobin responses are higher in the male group. Additionally, male group exhibited the stronger connectivity in the PFC regions. In the result of lateralization, leftward dominant was observed in the male group but bilateral dominance in the female group. Finally, the 11 channels of the inferior PFC regions (corresponding to the region of Brodmann area 45) are significant different with spectrum analysis. Our findings suggest that the resting-state fOT method can provide high potential to apply to clinical neuroscience for several gender-related mental disorders diagnosis.
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Ectopic DNMT3L triggers assembly of a repressive complex for retroviral silencing in somatic cells.
J. Virol.
PUBLISHED: 07-02-2014
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Mammalian genomes are replete with retrotransposable elements, including endogenous retroviruses. DNA methyltransferase 3-like (DNMT3L) is an epigenetic regulator expressed in prospermatogonia, growing oocytes, and embryonic stem (ES) cells. Here, we demonstrate that DNMT3L enhances the interaction of repressive epigenetic modifiers, including histone deacetylase 1 (HDAC1), SET domain, bifurcated 1 (SETDB1), DNA methyltransferase 3A (DNMT3A), and tripartite motif-containing protein 28 (TRIM28; also known as TIF1? and KAP1) in ES cells and orchestrates retroviral silencing activity with TRIM28 through mechanisms including, but not limited to, de novo DNA methylation. Ectopic expression of DNMT3L in somatic cells causes methylation-independent retroviral silencing activity by recruitment of the TRIM28/HDAC1/SETDB1/DNMT3A/DNMT3L complex to newly integrated Moloney murine leukemia virus (Mo-MuLV) proviral DNA. Concurrent with this recruitment, we also observed the accumulation of histone H3 lysine 9 trimethylation (H3K9me3) and heterochromatin protein 1 gamma (HP1?), as well as reduced H3K9 and H3K27 acetylation at Mo-MuLV proviral sequences. Ectopic expression of DNMT3L in late-passage mouse embryonic fibroblasts (MEFs) recruited cytoplasmically localized HDAC1 to the nucleus. The formation of this epigenetic modifying complex requires interaction of DNMT3L with DNMT3A as well as with histone H3. In fetal testes at embryonic day 17.5, endogenous DNMT3L also enhanced the binding among TRIM28, DNMT3A, SETDB1, and HDAC1. We propose that DNMT3L may be involved in initiating a cascade of repressive epigenetic modifications by assisting in the preparation of a chromatin context that further attracts DNMT3A-DNMT3L binding and installs longer-term DNA methylation marks at newly integrated retroviruses.
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Nucleophilic conjugate 1,3-addition of phosphines to oligoynoates.
Chem. Commun. (Camb.)
PUBLISHED: 06-20-2014
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Herein we have elucidated unusual and unique nucleophilic conjugate 1,3-addition reactions of surveyed oligoynoates toward phosphines through spectroscopic and single crystal X-ray diffraction analyses of three-component reaction products of oligoynoates, phosphines and aldehydes.
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Discovery and optimization of 5-fluoro-4,6-dialkoxypyrimidine GPR119 agonists.
Bioorg. Med. Chem. Lett.
PUBLISHED: 06-05-2014
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A series of 5-fluoro-4,6-dialkoxypyrimidine GPR119 modulators were discovered and optimized for in vitro agonist activity. A lead molecule was identified that has improved agonist efficacy relative to our clinical compound (APD597) and possesses reduced CYP2C9 inhibitory potential. This optimized lead was found to be efficacious in rodent models of glucose control both alone and in combination with a Dipeptidyl peptidase-4 (DPP-4) inhibitor.
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One-pot synthesis of highly substituted polyheteroaromatic compounds by rhodium(III)-catalyzed multiple C-H activation and annulation.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 05-11-2014
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A new method for the synthesis of highly substituted naphthyridine-based polyheteroaromatic compounds in high yields proceeds through rhodium(III)-catalyzed multiple C-H bond cleavage and C-C and C-N bond formation in a one-pot process. Such highly substituted polyheteroaromatic compounds have attracted much attention because of their unique ?-conjugation, which make them suitable materials for organic semiconductors and luminescent materials. Furthermore, a possible mechanism, which involves multiple chelation-assisted ortho C-H activation, alkyne insertion, and reductive elimination, is proposed for this transformation.
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Aurora-A signaling is activated in advanced stage of squamous cell carcinoma of head and neck cancer and requires osteopontin to stimulate invasive behavior.
Oncotarget
PUBLISHED: 05-10-2014
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The clinical significances, cellular effects, and molecular mechanisms by which Aurora-A mediate its invasive effects in HNSCC are still unclear. Here, we found that Aurora-A expression is significantly higher in tumor tissues on 14-microarray of HNSCC in Oncomine-databases. The activity of Aurora-A was not only found in HNSCC specimens, but also significantly correlated with advanced-T-classification, positive-N-classification, TNM-stage and the poor 5-year survival rate. HNSCC-microarray profile showed that osteopontin and Aurora-A exhibited positive correlation. Stimulation of HNC cells with osteopontin results in an increase in Aurora-A expression where localized at the centrosome. Functionally, Aurora-A had the abilities to stimulate cell motility in HNC cells through increase ERK1/2 activity under osteopontin stimulation. Conversely, depletion of Aurora-A expression by siRNAs suppressed ERK1/2 activity as well as inhibition of cell invasiveness. Treatment with anti-CD44 antibodies in HNC cells not only caused a decrease of mRNA/protein of Aurora-A and ERK1/2 activity upon osteopontin stimulation, but also affected the abilities of Aurora-A-elicited cell motility. Finally, immunohistochemical/Western-blotting analysis of human aggressive HNSCC specimens showed a significant positively correlation between osteopontin-Aurora-A and ERK1/2. These findings suggest that Aurora-A is not only an important prognostic factor but also a new therapeutic target in the osteopontin/CD44/ERK pathway for HNSCC treatment.
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A Phase 3 Randomized Double-Blind Comparison of Ceftobiprole Medocaril Versus Ceftazidime Plus Linezolid for the Treatment of Hospital-Acquired Pneumonia.
Clin. Infect. Dis.
PUBLISHED: 04-09-2014
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?Ceftobiprole, the active moiety of ceftobiprole medocaril, is a novel broad-spectrum cephalosporin, with bactericidal activity against a wide range of gram-positive bacteria, including Staphylococcus aureus (including methicillin-resistant strains) and penicillin- and ceftriaxone-resistant pneumococci, and gram-negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa.
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The impact of central line insertion bundle on central line-associated bloodstream infection.
BMC Infect. Dis.
PUBLISHED: 03-31-2014
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Knowledge about the impact of each central line insertion bundle on central line-associated bloodstream infection (CLABSI) is limited.
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Diffuser-aided time-domain diffuse optical imaging: a phantom study.
J Biomed Opt
PUBLISHED: 02-26-2014
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We present the first experimental results of time-resolved diffuser-aided diffuse optical imaging (DADOI) method in this paper. A self-manufactured diffuser plate was inserted between the optode and the surface of a scattering medium. The diffuser was utilized to enhance the multiple scattering that destroys the image information for baseline measurement of turbid medium. Therefore, the abnormality can be detected with the modified optical density calculation. The time-domain DADOI method can provide better imaging contrast and simpler imaging than the conventional diffuse optical tomography measurement. Besides, it also reveals rich depth information with temporal responses. Therefore, the DADOI offers a great potential to detect the breast tumor and chemotherapy monitoring in clinical diagnosis.
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Trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus causing invasive infections in Taiwan: results from the Tigecycline in vitro Surveillance in Taiwan (TIST) study, 2006-2010.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 02-19-2014
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This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ?1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time.
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An audit of cancer of unknown primary notifications: A cautionary tale for population health research using cancer registry data.
Cancer Epidemiol
PUBLISHED: 02-18-2014
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Cancer of unknown primary (CUP) is a common cancer yet little is known about the reliability of incidence data.
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Suppression of the SOX2 neural effector gene by PRDM1 promotes human germ cell fate in embryonic stem cells.
Stem Cell Reports
PUBLISHED: 02-11-2014
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The mechanisms of transcriptional regulation underlying human primordial germ cell (PGC) differentiation are largely unknown. The transcriptional repressor Prdm1/Blimp-1 is known to play a critical role in controlling germ cell specification in mice. Here, we show that PRDM1 is expressed in developing human gonads and contributes to the determination of germline versus neural fate in early development. We show that knockdown of PRDM1 in human embryonic stem cells (hESCs) impairs germline potential and upregulates neural genes. Conversely, ectopic expression of PRDM1 in hESCs promotes the generation of cells that exhibit phenotypic and transcriptomic features of early PGCs. Furthermore, PRDM1 suppresses transcription of SOX2. Overexpression of SOX2 in hESCs under conditions favoring germline differentiation skews cell fate from the germline to the neural lineage. Collectively, our results demonstrate that PRDM1 serves as a molecular switch to modulate the divergence of neural or germline fates through repression of SOX2 during human development.
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Clinical features of patients with carbapenem nonsusceptible Klebsiella pneumoniae and Escherichia coli in intensive care units: A nationwide multicenter study in Taiwan.
J Microbiol Immunol Infect
PUBLISHED: 01-16-2014
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Patients in intensive care units (ICUs) are especially prone to colonization and infection by carbapenem-resistant Enterobacteriaceae. We conducted a multicenter investigation to study the clinical and microbiological characteristics of patients with carbapenem nonsusceptible Klebsiella pneumoniae and Escherichia coli in ICUs of Taiwanese hospitals.
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Discriminant analysis of functional optical topography for schizophrenia diagnosis.
J Biomed Opt
PUBLISHED: 01-15-2014
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Abnormal prefrontal function plays a central role in the cognition deficits of schizophrenic patients; however, the character of the relationship between discriminant analysis and prefrontal activation remains undetermined. Recently, evidence of low prefrontal cortex (PFC) activation in individuals with schizophrenia has also been found during verbal fluency tests (VFT) and other cognitive tests with several neuroimaging methods. The purpose of this study is to assess the hemodynamic changes of the PFC and discriminant analysis between schizophrenia patients and healthy controls during VFT task by utilizing functional optical topography. A total of 99 subjects including 53 schizophrenic patients and 46 age- and gender-matched healthy controls were studied. The results showed that the healthy group had larger activation in the right and left PFC than in the middle PFC. Besides, the schizophrenic group showed weaker task performance and lower activation in the whole PFC than the healthy group. The result of the discriminant analysis showed a significant difference with P value<0.001 in six channels (CH 23, 29, 31, 40, 42, 52) between the schizophrenic and healthy groups. Finally, 68.69% and 71.72% of subjects are correctly classified as being schizophrenic or healthy with all 52 channels and six significantly different channels, respectively. Our findings suggest that the left PFC can be a feature region for discriminant analysis of schizophrenic diagnosis.
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Cytomegalovirus colitis in intensive care unit patients: difficulties in clinical diagnosis.
J Crit Care
PUBLISHED: 01-05-2014
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Cytomegalovirus (CMV) infection occurs increasingly in critically ill patients in intensive care units (ICUs). We reported CMV colitis which has rarely been recognized in the ICU patients.
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Virulence Diversity among Bacteremic Aeromonas Isolates: Ex Vivo, Animal, and Clinical Evidences.
PLoS ONE
PUBLISHED: 01-01-2014
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The objective of this study was to compare virulence among different Aeromonas species causing bloodstream infections.
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The impact of inadequate terminal disinfection on an outbreak of imipenem-resistant Acinetobacter baumannii in an intensive care unit.
PLoS ONE
PUBLISHED: 01-01-2014
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This study was conducted to investigate an outbreak caused by imipenem-resistant Acinetobacter baumannii (IRAB) in a medical intensive care unit (ICU) in a regional hospital.
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Prototheca Algaemia: a Rare but Fatal Opportunistic Infection among Immunocompromised Individuals.
Jpn. J. Infect. Dis.
PUBLISHED: 11-26-2013
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Infections due to Prototheca spp. are ubiquitous in nature, occurring in both immunocompetent and immunocompromised patients. The study cohort consisted of 14 cases of Prototheca algaemia reported over the past 5 decades and 2 recent cases from study hospitals. Prototheca wickerhamii was the most common species. The overall mortality rate was 62.5%. Prototheca algaemia, a healthcare-associated infection, was observed in immunocompromised patients and was associated with a poor prognosis.
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One-pot formation of fluorescent ?-lactams having an ?-phosphorus ylide moiety through three-component ?(?)-Michael reactions of phosphines with an enyne and N-tosyl aldimines.
Org. Biomol. Chem.
PUBLISHED: 11-11-2013
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We demonstrate a straightforward synthesis of ?-lactams possessing an ?-phosphorus ylide moiety from assembly of phosphines, N-tosyl aldimines and an enyne through an initial ?(?)-attack of phosphines to an enyne in up to 79% yield. The investigated multicomponent reaction tolerates a variety of triarylphosphines and electron-poor aldimines to give ?-lactams in one pot. One of the lactams, with the tri(p-tol)phosphine and 4-cyanophenyl moiety, exhibits fluorescence emission at 447 nm with a quantum yield of 0.11.
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One pot synthesis of bioactive benzopyranones through palladium-catalyzed C-H activation and CO insertion into 2-arylphenols.
Chem. Commun. (Camb.)
PUBLISHED: 11-11-2013
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Palladium-catalyzed oxidative carbonylation of 2-arylphenols through C-H bond activation and C-C and C-O bond formation under acid-base free and mild conditions has been developed. The reaction tolerates a variety of substrates and provides biologically important benzopyranone derivatives in up to 87% isolated yield.
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Integrative transcriptome sequencing identifies trans-splicing events with important roles in human embryonic stem cell pluripotency.
Genome Res.
PUBLISHED: 10-16-2013
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Trans-splicing is a post-transcriptional event that joins exons from separate pre-mRNAs. Detection of trans-splicing is usually severely hampered by experimental artifacts and genetic rearrangements. Here, we develop a new computational pipeline, TSscan, which integrates different types of high-throughput long-/short-read transcriptome sequencing of different human embryonic stem cell (hESC) lines to effectively minimize false positives while detecting trans-splicing. Combining TSscan screening with multiple experimental validation steps revealed that most chimeric RNA products were platform-dependent experimental artifacts of RNA sequencing. We successfully identified and confirmed four trans-spliced RNAs, including the first reported trans-spliced large intergenic noncoding RNA ("tsRMST"). We showed that these trans-spliced RNAs were all highly expressed in human pluripotent stem cells and differentially expressed during hESC differentiation. Our results further indicated that tsRMST can contribute to pluripotency maintenance of hESCs by suppressing lineage-specific gene expression through the recruitment of NANOG and the PRC2 complex factor, SUZ12. Taken together, our findings provide important insights into the role of trans-splicing in pluripotency maintenance of hESCs and help to facilitate future studies into trans-splicing, opening up this important but understudied class of post-transcriptional events for comprehensive characterization.
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KPC-2-encoding plasmids from Escherichia coli and Klebsiella pneumoniae in Taiwan.
J. Antimicrob. Chemother.
PUBLISHED: 10-11-2013
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Two plasmids carrying blaKPC-2 isolated from carbapenem-resistant Escherichia coli (CR-EC) and carbapenem-resistant Klebsiella pneumoniae (CR-KP), respectively, were completely sequenced. The CR-KP strain was selected from an outbreak in 2012, and the CR-EC strain was the first blaKPC-2-carrying E. coli identified in the same carbapenem resistance monitoring programme in Taiwan.
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Updated molecular epidemiology of carbapenem-non-susceptible Escherichia coli in Taiwan: first identification of KPC-2 or NDM-1-producing E. coli in Taiwan.
BMC Infect. Dis.
PUBLISHED: 08-26-2013
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The global spread and increasing incidence of carbapenem-resistant Enterobacteriaceae have resulted in treatment and public health concerns. Here, we present an investigation of the molecular mechanisms and clonality of carbapenem-non-susceptible Escherichia coli (CnSEC) based on a nationwide survey in Taiwan.
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In vitro efficacies and resistance profiles of rifampin-based combination regimens for biofilm-embedded methicillin-resistant Staphylococcus aureus.
Antimicrob. Agents Chemother.
PUBLISHED: 08-19-2013
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To compare the in vitro antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant Staphylococcus aureus (MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.
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LHX2 regulates the neural differentiation of human embryonic stem cells via transcriptional modulation of PAX6 and CER1.
Nucleic Acids Res.
PUBLISHED: 06-26-2013
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The LIM homeobox 2 transcription factor Lhx2 is known to control crucial aspects of neural development in various species. However, its function in human neural development is still elusive. Here, we demonstrate that LHX2 plays a critical role in human neural differentiation, using human embryonic stem cells (hESCs) as a model. In hESC-derived neural progenitors (hESC-NPs), LHX2 was found to be expressed before PAX6, and co-expressed with early neural markers. Conditional ectopic expression of LHX2 promoted neural differentiation, whereas disruption of LHX2 expression in hESCs significantly impaired neural differentiation. Furthermore, we have demonstrated that LHX2 regulates neural differentiation at two levels: first, it promotes expression of PAX6 by binding to its active enhancers, and second, it attenuates BMP and WNT signaling by promoting expression of the BMP and WNT antagonist Cerberus 1 gene (CER1), to inhibit non-neural differentiation. These findings indicate that LHX2 regulates the transcription of downstream intrinsic and extrinsic molecules that are essential for early neural differentiation in human.
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Dental optical coherence tomography.
Sensors (Basel)
PUBLISHED: 05-28-2013
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This review paper describes the applications of dental optical coherence tomography (OCT) in oral tissue images, caries, periodontal disease and oral cancer. The background of OCT, including basic theory, system setup, light sources, spatial resolution and system limitations, is provided. The comparisons between OCT and other clinical oral diagnostic methods are also discussed.
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In vitro efficacy of fosfomycin-based combinations against clinical vancomycin-resistant Enterococcus isolates.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 04-09-2013
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Vancomycin-resistant (VR) enterococci (VRE) are increasingly important nosocomial pathogens, commonly causing catheter-related urinary tract infections or vascular catheter-related bloodstream infections. In this study, 10 Enterococcus faecium and 9 Enterococcus faecalis different pulsed-field gel electrophoresis genome-type VR clinical isolates were detected. The potential role of fosfomycin-based combination regimens for biofilm-related VRE infection is in vitro evaluated. Anti-VRE activities of fosfomycin, ampicillin, linezolid, minocycline, rifampicin, tigecycline, teicoplanin, vancomycin alone, or fosfomycin-based combinations were studied by time-kill method and a biofilm model. Of the fosfomycin-based combinations, a synergistic effect was particularly noted for teicoplanin against 89% of the VR E. faecalis isolates. In a biofilm model, only linezolid alone was able to reduce the bacterial loads, and the use of fosfomycin-based combinations, excluding rifampicin (40%), failed to enhance antibacterial activity against VR E. faecium. For E. faecalis, an inhibitory effect was evident using ampicillin alone or fosfomycin plus rifampicin (100%), tigecycline (56%), or teicoplanin (44%). However, an antagonistic effect was found for ampicillin plus fosfomycin against 2 of 3 of the VR E. faecalis isolates. The antibacterial activities of the drugs tested against VRE in vitro varied by species. Ampicillin exhibited potential activity against planktonic- and biofilm-embedded VR E. faecalis. Fosfomycin-based combinations may have enhanced antibacterial effects against VRE even in the biofilm model, and this observation warrants further clinical studies.
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Effect of routine esophageal screening in patients with head and neck cancer.
JAMA Otolaryngol Head Neck Surg
PUBLISHED: 03-23-2013
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Transnasal esophagoscopy or pandoscopy to conduct a tumor survey is routinely recommended for patients with head and neck squamous cell carcinoma (HNSCC). Despite this recommendation, the effect of routine esophageal screening remains unclear.
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Vitamin E facilitates the inactivation of the kinase Akt by the phosphatase PHLPP1.
Sci Signal
PUBLISHED: 03-21-2013
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Vitamin E is a fat-soluble vitamin with antioxidant properties. Tocopherols are the predominant form of vitamin E found in the diet and in supplements and have garnered interest for their potential cancer therapeutic and preventive effects, such as the dephosphorylation of Akt, a serine/threonine kinase with a pivotal role in cell growth, survival, and metabolism. Dephosphorylation of Akt at Ser473 substantially reduces its catalytic activity and inhibits downstream signaling. We found that the mechanism by which ?-tocopherol and ?-tocopherol facilitate this site-specific dephosphorylation of Akt was mediated through the pleckstrin homology (PH) domain-dependent recruitment of Akt and PHLPP1 (PH domain leucine-rich repeat protein phosphatase, isoform 1) to the plasma membrane. We structurally optimized these tocopherols to obtain derivatives with greater in vitro potency and in vivo tumor-suppressive activity in two prostate xenograft tumor models. Binding affinities for the PH domains of Akt and PHLPP1 were greater than for other PH domain-containing proteins, which may underlie the preferential recruitment of these proteins to membranes containing tocopherols. Molecular modeling revealed the structural determinants of the interaction with the PH domain of Akt that may inform strategies for continued structural optimization. By describing a mechanism by which tocopherols facilitate the dephosphorylation of Akt at Ser473, we provide insights into the mode of antitumor action of tocopherols and a rationale for the translational development of tocopherols into novel PH domain-targeted Akt inhibitors.
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Palladium-catalyzed oxidative insertion of carbon monoxide to N-sulfonyl-2-aminobiaryls through C-H bond activation: access to bioactive phenanthridinone derivatives in one pot.
Org. Lett.
PUBLISHED: 03-11-2013
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Palladium-catalyzed oxidative carbonylation of N-sulfonyl-2-aminobiaryls through C-H bond activation and C-C, C-N bond formation under TFA-free and milder conditions has been developed. The reaction tolerates a variety of substrates and provides biologically important phenanthridinone derivatives in yields up to 94%.
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The expression of activin receptor-like kinase 1 among patients with head and neck cancer.
Otolaryngol Head Neck Surg
PUBLISHED: 02-27-2013
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We investigated the expression and clinical significance of activin receptor-like kinase 1 (ACVRL1) in patients with head and neck squamous cell carcinoma (HNSCC).
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?(?)-Michael addition of alkyl amines to dimethyl (E)-hex-2-en-4-ynedioate: synthesis of ?,?-dehydroamino acid derivatives.
Molecules
PUBLISHED: 02-07-2013
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The direct nucleophilic addition of alkyl amines to the ?(?)-carbon atom of dimethyl (E)-hex-2-en-4-ynedioate to generate ?,?-dehydroamino acid derivatives is reported. Herein, we have studied the reactivity of various primary and secondary alkyl amines in the ?-selective nucleophilic conjugate addition to conjugated dimethyl (E)-hex-2-en-4-ynedioate. The reaction with primary alkyl amines gives only the (2E,4E)-stereoisomer, while that with secondary alkyl amines gives the (2E,4E) and (2Z,4E)-stereoisomers of dimethyl (2-alkylamino)-muconic ester.
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Biological evaluation of 9-[(6-chloropyridin-4-yl)methyl]-9H-carbazole-3-carbinol as an anticancer agent.
Oncol. Rep.
PUBLISHED: 01-29-2013
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Most conventional anticancer drugs exert either anti-proliferation or anti-angiogenesis activity. Recently, searching for potential multi-target agents has become an alternative strategy for cancer treatment. Several structurally different carbazole alkaloids from either natural or synthesized sources represent an important and heterogeneous class of anticancer agents. In the present study, we investigated the anticancer activity of a novel synthetic carbazole derivative, 9-[(6-chloropyridin-4-yl)methyl]-9H-carbazole-3-carbinol (HYL-6d), which is structurally different from other previously characterized carbazoles. HYL-6d-treated human breast cancer MCF-7 cells exhibited an increased population arrested at the sub-G1 and S phases, as well as an increase of p53 and decrease of cyclin D1, A and CDK2. Also, HYL-6d treatment induced MCF-7 cell apoptosis and this was accompanied by a decreased expression of Bcl-2, increased levels of p53 and Bcl-XS and the activation of caspase-9. Experimental results from human umbilical vascular endothelial cells (HUVECs) showed that HYL-6d also exerted its anti-angiogenic activity in HUVECs by inhibiting cell proliferation, migration, and tube formation induced by VEGF- or bFGF in vitro. In summary, the data indicate that HYL-6d exhibits both cytotoxic effects against human cancer cells and anti-angiogenic activities, which make it a potential therapeutic drug for cancer treatment.
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Trends in the antimicrobial susceptibilities and serotypes of Streptococcus pneumoniae: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010.
Int. J. Antimicrob. Agents
PUBLISHED: 01-26-2013
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Isolates of Streptococcus pneumoniae (n = 530) were collected from 20 hospitals in different parts of Taiwan from 2006 to 2010. MICs to 16 antimicrobial agents were determined by broth dilution method and serotypes were identified by latex agglutination. Based on meningitis (non-meningitis) criteria established by the CLSI, 11.7% (63.2%) of all isolates were susceptible to penicillin and 46.0% (83.8%) were susceptible to ceftriaxone. Of the isolates, 94.3% were non-susceptible to azithromycin and 5.8% and 7.2% were non-susceptible to moxifloxacin and levofloxacin, respectively. Susceptibility to penicillin by meningitis criteria increased significantly (P = 0.0012) with year, and that to clindamycin and amoxicillin/clavulanic acid declined significantly (P < 0.05). Six major serotypes were found, namely 19F (24.0%), 23F (18.5%), 14 (13.6%), 6B (12.5%), 19A (7.5%) and 3 (5.1%). Prevalence of serotypes 19F and 14 remained stationary, that of serotype 6B decreased significantly (P < 0.0001) and that of serotype 19A increased significantly (P < 0.0001) with year. The coverage rate of PCV-7 among the pneumococcal isolates declined from 80.5% in 2006 to 50% in 2010 (P < 0.0001) and that of PCV-13 declined from 91.5% in 2009 to 75% in 2010. The non-susceptibility rate to levofloxacin was highest among serotype 23F isolates (13.3%) and lowest among serotype 19A isolates (2.5%). Rates of resistance to the four agents penicillin, ceftriaxone, azithromycin and clindamycin were highest among serotype 19A isolates (70.0%) and 23F isolates (49.0%). All serotype 3 isolates were susceptible to four of the most commonly used antibiotics (penicillin, ceftriaxone, azithromycin and levofloxacin).
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Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 01-20-2013
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Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m(2)/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.
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Acid aspiration provokes the pneumonia caused by multidrug-resistant Acinetobacter baumannii in BALB/c mice.
Int. J. Infect. Dis.
PUBLISHED: 01-15-2013
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To determine whether acid aspiration provokes the development of multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia in its host.
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Gestational ingestion of oxidized frying oil by C57BL/6J mice differentially affects the susceptibility of the male and female offspring to diet-induced obesity in adulthood.
J. Nutr.
PUBLISHED: 01-09-2013
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The aim of this study was to investigate whether maternal ingestion of oxidized frying oil (OFO) during pregnancy influences the susceptibility to diet-induced obesity (DIO) of the adult offspring. Pregnant C57BL/6J mice were fed either a control diet [10% fresh soybean oil (SO)] or an OFO-containing diet (10% OFO) throughout the entire gestational period. After parturition, all pups were nursed by SO-fed dams for 3 wk, weaned onto a nonpurified standard diet for 4 wk, and shifted to a high-fat diet (29% butter + 1% SO) for 5 wk. Consequently, 4 groups of offspring were obtained, consisting of the male (m) or female (f) offspring of dams fed the OFO diet (OFO-m and OFO-f) or the SO diet (SO-m and SO-f). At pregnancy d 18, higher amounts (P < 0.05) of mRNA for PPAR? target genes were found in the liver of the OFO-fed dams and their fetuses than in their SO controls. Although all pups were raised under the same conditions in postnatal life, a comparison based on the gender of pups from dams fed the different diets showed that adult OFO-f mice were prone to DIO, whereas adult OFO-m mice were resistant. The adult OFO-m mice also had higher expression of PPAR? target genes in the liver and white adipose tissue (WAT) and of thermogenic genes in the WAT than adult SO-m mice, whereas adult OFO-f and SO-f mice did not differ. We conclude that uterine PPAR? activation caused by maternal OFO ingestion affects hepatic PPAR? activity and adipose thermogenic capacity and contributes to the differential susceptibility to DIO in the male and female offspring in adulthood.
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Recognition of hydrogen isotopomers by an open-cage fullerene.
Philos Trans A Math Phys Eng Sci
PUBLISHED: 01-01-2013
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We present our study on the recognition of hydrogen isotopes by an open-cage fullerene through determination of binding affinity of isotopes H?/HD/D? with the open-cage fullerene and comparison of their relative molecular sizes through kinetic-isotope-release experiments. We took advantage of isotope H?/D? exchange that generated an equilibrium mixture of H?/HD/D? in a stainless steel autoclave to conduct high-pressure hydrogen insertion into an open-cage fullerene. The equilibrium constants of three isotopes with the open-cage fullerene were determined at various pressures and temperatures. Our results show a higher equilibrium constant for HD into open-cage fullerene than the other two isotopomers, which is consistent with its dipolar nature. D? molecule generally binds stronger than H? because of its heavier mass; however, the affinity for H? becomes larger than D? at lower temperature, when size effect becomes dominant. We further investigated the kinetics of H?/HD/D? release from open-cage fullerene, proving their relative escaping rates. D? was found to be the smallest and H? the largest molecule. This notion has not only supported the observed inversion of relative binding affinities between H? and D?, but also demonstrated that comparison of size difference of single molecules through non-convalent kinetic-isotope effect was applicable.
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National surveillance study on carbapenem non-susceptible Klebsiella pneumoniae in Taiwan: the emergence and rapid dissemination of KPC-2 carbapenemase.
PLoS ONE
PUBLISHED: 01-01-2013
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The global spread and increasing incidence of carbapenem non-susceptible Klebsiella pneumoniae (CnSKP) has made its treatment difficult, increasing the mortality. To establish nationwide data on CnSKP spread and carbapenem-resistance mechanisms, we conducted a national surveillance study in Taiwanese hospitals.
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Functional Role of mTORC2 versus Integrin-Linked Kinase in Mediating Ser473-Akt Phosphorylation in PTEN-Negative Prostate and Breast Cancer Cell Lines.
PLoS ONE
PUBLISHED: 01-01-2013
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Although the rictor-mTOR complex (mTORC2) has been shown to act as phosphoinositide-dependent kinase (PDK)2 in many cell types, other kinases have also been implicated in mediating Ser473-Akt phosphorylation. Here, we demonstrated the cell line specificity of integrin-linked kinase (ILK) versus mTORC2 as PDK2 in LNCaP and PC-3 prostate and MDA-MB-468 breast cancer cells, of which the PTEN-negative status allowed the study of Ser473-Akt phosphorylation independent of external stimulation. PC-3 and MDA-MB-468 cells showed upregulated ILK expression relative to LNCaP cells, which expressed a high abundance of mTOR. Exposure to Ku-0063794, a second-generation mTOR inhibitor, decreased Ser473-Akt phosphorylation in LNCaP cells, but not in PC-3 or MDA-MB-468 cells. In contrast, treatment with T315, a novel ILK inhibitor, reduced the phosphorylation of Ser473-Akt in PC-3 and MDA-MB-468 cells without affecting that in LNCaP cells. This cell line specificity was verified by comparing Ser473-Akt phosphorylation status after genetic knockdown of rictor, ILK, and other putative Ser-473-Akt kinases. Genetic knockdown of rictor, but not ILK or the other kinases examined, inhibited Ser473-Akt phosphorylation in LNCaP cells. Conversely, PC-3 and MDA-MB-468 cells were susceptible to the effect of ILK silencing on Ser473-Akt phosphorylation, while knockdown of rictor or any of the other target kinases had no appreciable effect. Co-immunoprecipitation analysis demonstrated the physical interaction between ILK and Akt in PC-3 cells, and T315 blocked ILK-mediated Ser473 phosphorylation of bacterially expressed Akt. ILK also formed complexes with rictor in PC-3 and MDA-MB-468 cells that were disrupted by T315, but such complexes were not observed in LNCaP cells. In the PTEN-functional MDA-MB-231 cell line, both T315 and Ku-0063794 suppressed EGF-induced Ser473-Akt phosphorylation. Inhibition of ILK by T315 or siRNA-mediated knockdown suppressed epithelial-mesenchymal transition in MDA-MB-468 and PC-3 cells. Thus, we hypothesize that ILK might bestow growth advantage and metastatic potential in the course of tumor progression.
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Trends in the susceptibility of clinically important resistant bacteria to tigecycline: results from the Tigecycline In Vitro Surveillance in Taiwan study, 2006 to 2010.
Antimicrob. Agents Chemother.
PUBLISHED: 12-27-2011
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The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n = 423), vancomycin-resistant enterococci (VRE) (n = 219), extended-spectrum ?-lactamase (ESBL)-producing Escherichia coli (n = 1,141), ESBL-producing Klebsiella pneumoniae (n = 1,330), Acinetobacter baumannii (n = 1,645), and Stenotrophomonas maltophilia (n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC(90), 0.03 ?g/ml), and only one MRSA isolate (MIC(90), 0.5 ?g/ml) and three VRE isolates (MIC(90), 0.125 ?g/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC(90), 0.5 ?g/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC(90), 2 ?g/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC(90), 4 ?g/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii.
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Agreement assessment of tigecycline susceptibilities determined by the disk diffusion and broth microdilution methods among commonly encountered resistant bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2008
Antimicrob. Agents Chemother.
PUBLISHED: 12-12-2011
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The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum ?-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 ?g/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.
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Using a nurse invented T-Bar device in a rehabilitation program improved the range of motion for rotator cuff repair patients.
J Clin Nurs
PUBLISHED: 11-15-2011
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This study investigates the effects on patient outcomes of using a T-bar in rehabilitation programs in shoulder arthroscopic surgical procedure patients.
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Bacteremia due to extended-spectrum-?-lactamase-producing Aeromonas spp. at a medical center in Southern Taiwan.
Antimicrob. Agents Chemother.
PUBLISHED: 10-03-2011
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Although extended-spectrum-?-lactamase (ESBL)-producing aeromonads have been increasingly reported in recent years, most of them were isolates from case reports or environmental isolates. To investigate the prevalence of ESBL producers among Aeromonas blood isolates and the genes encoding ESBLs, consecutive nonduplicate Aeromonas blood isolates collected at a medical center in southern Taiwan from March 2004 to December 2008 were studied. The ESBL phenotypes were examined by clavulanate combination disk test and the cefepime-clavulanate ESBL Etest. The presence of ESBL-encoding genes, including bla(TEM), bla(PER), bla(CTX-M), and bla(SHV) genes, was evaluated by PCR and sequence analysis. The results showed that 4 (2.6%) of 156 Aeromonas blood isolates, 1 Aeromonas hydrophila isolate and 3 Aeromonas caviae isolates, expressed an ESBL-producing phenotype. The ESBL gene in two A. caviae isolates was bla(PER-3), which was located in both chromosomes and plasmids, as demonstrated by Southern hybridization. Of four patients with ESBL-producing Aeromonas bacteremia, two presented with catheter-related phlebitis and the other two with primary bacteremia. Three patients had been treated with initial noncarbapenem ?-lactams for 5 to 10 days, and all survived. In conclusion, ESBL producers exist among Aeromonas blood isolates, and clinical suspicion of ESBL production should be raised in treating infections due to cefotaxime-resistant Aeromonas isolates.
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Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Hum. Mol. Genet.
PUBLISHED: 09-15-2011
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Pompe disease is caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene, which encodes GAA. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease-induced pluripotent stem cells (PomD-iPSCs) from two patients with different GAA mutations and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to recombinant human GAA reversed the major pathologic phenotypes. Furthermore, l-carnitine treatment reduced defective cellular respiration in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria-related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for the development of novel therapeutic strategies for Pompe disease.
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Comparative evaluation of intratracheal colistimethate sodium, imipenem, and meropenem in BALB/c mice with carbapenem-resistant Acinetobacter baumannii pneumonia.
Int. J. Infect. Dis.
PUBLISHED: 09-08-2011
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The identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB).
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Identification and characterization of a novel integrin-linked kinase inhibitor.
J. Med. Chem.
PUBLISHED: 08-24-2011
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Integrin-linked kinase (ILK) represents a relevant target for cancer therapy in light of its role in promoting oncogenesis and tumor progression. Through the screening of an in-house focused compound library, we identified N-methyl-3-(1-(4-(piperazin-1-yl)phenyl)-5-(4-(trifluoromethyl)-[1,1-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide (22) as a novel ILK inhibitor (IC(50), 0.6 ?M), which exhibited high in vitro potency against a panel of prostate and breast cancer cell lines (IC(50), 1-2.5 ?M), while normal epithelial cells were unaffected. Compound 22 facilitated the dephosphorylation of Akt at Ser-473 and other ILK targets, including glycogen synthase kinase-3? and myosin light chain. Moreover, 22 suppressed the expression of the transcription/translation factor YB-1 and its targets HER2 and EGFR in PC-3 cells, which could be rescued by the stable expression of constitutively active ILK. Evidence indicates that 22 induced autophagy and apoptosis, both of which were integral to its antiproliferative activity. Together, this broad spectrum of mechanisms underlies the therapeutic potential of 22 in cancer treatment, which is manifested by its in vivo efficacy as a single oral agent in suppressing PC-3 xenograft tumor growth.
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Subgingival calculus imaging based on swept-source optical coherence tomography.
J Biomed Opt
PUBLISHED: 08-03-2011
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We characterized and imaged dental calculus using swept-source optical coherence tomography (SS-OCT). The refractive indices of enamel, dentin, cementum, and calculus were measured as 1.625 ± 0.024, 1.534 ± 0.029, 1.570 ± 0.021, and 2.097 ± 0.094, respectively. Dental calculus leads strong scattering properties, and thus, the region can be identified from enamel with SS-OCT imaging. An extracted human tooth with calculus is covered with gingiva tissue as an in vitro sample for tomographic imaging.
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Toll-like receptor 3-mediated tumor invasion in head and neck cancer.
Oral Oncol.
PUBLISHED: 08-01-2011
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Chronic inflammation associated with some infectious agents can lead to cancer. The Toll-like receptor (TLR) family is one of the largest and best-studied families of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA and is a major effector of the immune response against viral pathogens.
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Epithelial cell adhesion molecule (EpCAM) complex proteins promote transcription factor-mediated pluripotency reprogramming.
J. Biol. Chem.
PUBLISHED: 07-28-2011
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Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that is highly expressed in embryonic stem cells (ESCs) and its role in maintenance of pluripotency has been suggested previously. In epithelial cancer cells, activation of the EpCAM surface-to-nucleus signaling transduction pathway involves a number of membrane proteins. However, their role in somatic cell reprogramming is still unknown. Here we demonstrate that EpCAM and its associated protein, Cldn7, play a critical role in reprogramming. Quantitative RT-PCR analysis of Oct4, Sox2, Klf4, and c-Myc (OSKM) infected mouse embryonic fibroblasts (MEFs) indicated that EpCAM and Cldn7 were up-regulated during reprogramming. Analysis of numbers of alkaline phosphatase- and Nanog-positive clones, and the expression level of pluripotency-related genes demonstrated that inhibition of either EpCAM or Cldn7 expression resulted in impairment in reprogramming efficiency, whereas overexpression of EpCAM, EpCAM plus Cldn7, or EpCAM intercellular domain (EpICD) significantly enhanced reprogramming efficiency in MEFs. Furthermore, overexpression of EpCAM or EpICD significantly repressed the expression of p53 and p21 in the reprogramming MEFs, and both EpCAM and EpICD activated the promoter activity of Oct4. These observations suggest that EpCAM signaling may enhance reprogramming through up-regulation of Oct4 and possible suppression of the p53-p21 pathway. In vitro and in vivo characterization indicated that the EpCAM-reprogrammed iPSCs exhibited similar molecular and functional features to the mouse ESCs. In summary, our studies provide additional insight into the molecular mechanisms of reprogramming and suggest a more effective means of induced pluripotent stem cell generation.
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Fabrication of an asymmetric Bragg coupler-based polymeric filter with a single-grating waveguide.
Opt Express
PUBLISHED: 06-07-2011
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In this work, a first report on fabricating an asymmetric Bragg coupler-based filter on polymeric waveguides without input-waveguide grating was revealed. The fabrication process we developed was using holographic interference techniques, capillary effect, soft lithography, and micro molding process. The transmission dip of about -9.2 dB and the 3 dB transmission bandwidth of about 0.125 nm were obtained from a filter.
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Differential toll-like receptor 3 (TLR3) expression and apoptotic response to TLR3 agonist in human neuroblastoma cells.
J. Biomed. Sci.
PUBLISHED: 05-12-2011
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Toll-like receptor-3 (TLR-3) is a critical component of innate immune system against dsRNA viruses and is expressed in the central nervous system. However, it remains unknown whether TLR3 may serve as a therapeutic target in human neuroblastoma (NB).
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Diffuse optical multipatch technique for tissue oxygenation monitoring: clinical study in intensive care unit.
IEEE Trans Biomed Eng
PUBLISHED: 04-29-2011
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Diffuse optical multipatch technique is used to assess spatial variations in absorption and scattering in biological tissue, by monitoring changes in the concentration of oxyhemoglobin and deoxyhemoglobin. In our preliminary study, the temporal tracings of tissue oxygenation are measured using diffuse optical multipatch measurement and a venous occlusion test, employing normal subjects and ICU patients suffering from sepsis and heart failure. In experiments, obvious differences in tissue oxygenation signals were observed among all three groups. This paper discusses the physiological relevance of tissue oxygenation with respect to disease.
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Topical sucralfate for pain after oral CO2 laser surgery: a prospective, randomized, controlled trial.
Am J Otolaryngol
PUBLISHED: 04-14-2011
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The aim of this study was to assess the effect of topical sucralfate on postoperative pain scores and other secondary outcomes including the frequency and duration of analgesic use and postoperative bleeding episodes after CO(2) laser treatment of oral leukoplakia.
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Three-component and nonclassical reaction of phosphines with enynes and aldehydes: formation of ?-lactones featuring ?-phosphorus ylides.
Org. Lett.
PUBLISHED: 04-07-2011
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Inverted carbenoid species, generated from attack of phosphines at the ?(?)-carbon of hex-2-en-4-ynedioic acid dialkyl esters, react with aldehydes to give ?-lactones possessing an ?-phosphorus ylide moiety.
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Seroprevalence and severity of 2009 pandemic influenza A H1N1 in Taiwan.
PLoS ONE
PUBLISHED: 03-22-2011
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This study is to determine the seroprevalence of the pandemic influenza A H1N1 virus (pH1N1) in Taiwan before and after the 2009 pandemic, and to estimate the relative severity of pH1N1 infections among different age groups.
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Aorta fluorescence imaging by using confocal microscopy.
ISRN Cardiol
PUBLISHED: 03-17-2011
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The activated leukocyte attacked the vascular endothelium and the associated increase in VEcadherin number was observed in experiments. The confocal microscopic system with a prism-based wavelength filter was used for multiwavelength fluorescence measurement. Multiwavelength fluorescence imaging based on the VEcadherin within the aorta segment of a rat was achieved. The confocal microscopic system capable of fluorescence detection of cardiovascular tissue is a useful tool for measuring the biological properties in clinical applications.
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In vitro and in vivo intracellular killing effects of tigecycline against clinical nontyphoid Salmonella isolates using ceftriaxone as a comparator.
Antimicrob. Agents Chemother.
PUBLISHED: 03-14-2011
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Salmonella is an important, worldwide food-borne pathogen. Resistance to fluoroquinolones and cephalosporins has been increasingly reported, and new therapeutic agents are desperately needed. In this study, we evaluated the in vitro antimicrobial susceptibility of clinical nontyphoidal Salmonella isolates to tigecycline. Antibacterial activity of tigecycline, ceftriaxone, and ciprofloxacin were investigated by time-kill studies and the murine peritonitis model. The MIC??/MIC?? values of tigecycline, ceftriaxone, and ciprofloxacin against 76 Salmonella isolates were 0.25/0.5, 1/8, and 0.125/0.5 ?g/ml, respectively. The intracellular inhibitory activity of tigecycline at 0.5 ?g/ml (1 × MIC) against Salmonella isolates in human peripheral blood mononuclear cells was sustained for 24 h. In a mouse peritonitis model, tigecycline reduced the extracellular and intracellular bacterial counts from 10? CFU/ml and 10? CFU/ml, respectively, to an undetectable level within 96 h. The results were similar to those obtained with ceftriaxone. The survival rate of mice exposed to tigecycline after being infected by an inoculum of 1 × 10? CFU was 80%, and that of mice exposed to ceftriaxone was 100%. When the inoculum was increased to 1.3 × 10? CFU, the survival rate of mice treated by tigecycline was 20%, and that of mice exposed to ceftriaxone was 0% (P = 0.2). When a ceftriaxone- and ciprofloxacin-resistant but tigecycline-susceptible isolate was tested, mice treated by tigecycline had a higher survival rate than those treated by ceftriaxone (15/20 [75%] versus 6/20 [30%]; P = 0.011). Our results suggest that tigecycline is at least as effective as ceftriaxone for murine Salmonella infections and warrants further clinical investigations to delineate its potential against human Salmonella infections.
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Autoimmunity-related demyelination in infection by Japanese encephalitis virus.
J. Biomed. Sci.
PUBLISHED: 02-28-2011
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Japanese encephalitis (JE) virus is the most common cause of epidemic viral encephalitis in the world. The virus mainly infects neuronal cells and causes an inflammatory response after invasion of the parenchyma of the brain. The death of neurons is frequently observed, in which demyelinated axons are commonly seen. The mechanism that accounts for the occurrence of demyelination is ambiguous thus far. With a mouse model, the present study showed that myelin-specific antibodies appeared in sera, particularly in those mice with evident symptoms. Meanwhile, specific T cells proliferating in response to stimulation by myelin basic protein (MBP) was also shown in these mice. Taken together, our results suggest that autoimmunity may play an important role in the destruction of components, e.g., MBP, of axon-surrounding myelin, resulting in demyelination in the mouse brain after infection with the JE virus.
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Annulation of benzamides with [60]fullerene through palladium(II)-catalyzed C-H bond activation.
J. Org. Chem.
PUBLISHED: 02-23-2011
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Palladium-catalyzed heteroannulation of N-substituted benzamides with [60]fullerene, which proceeds through direct sp(2) C-H bond activation to form 7-membered ring pallada-intermediate with C(60), led to formation of [60]fulleroisoquinolinones in moderate to good yields (8-64% based on recovered C(60)). A plausible reaction pathway is proposed.
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