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Find video protocols related to scientific articles indexed in Pubmed.
DNA photocleavage in anaerobic conditions by a Ru(ii) complex: a new mechanism.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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[Ru(bpy)2(py-SO3)](+) (bpy = 2,2'-bipyridine and py-SO3 = pyridine-2-sulfonate) was found to undergo py-SO3 dissociation upon visible light irradiation (?470 nm) via Ru-O homolysis, producing reactive free radical species, and is thus able to not only photobind but also photocleave DNA in hypoxic conditions.
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Influence of gold-bipyridyl derivants on aggregation and disaggregation of the prion neuropeptide PrP106-126.
Metallomics
PUBLISHED: 10-03-2014
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Metal complexes can effectively inhibit the aggregation of amyloid peptides, such as A?, human islet amyloid polypeptide, and prion neuropeptide PrP106-126. Gold (Au) complexes exhibited better inhibition against PrP106-126 aggregation, particularly the Au-bipyridyl (bpy) complex; however, the role of different ligand configurations remains unclear. In the present study, three derivants of Au-bpy complexes, namely, [Au(Me2bpy)Cl2]Cl, [Au(t-Bu2bpy)Cl2]Cl, and [Au(Ph2bpy)Cl2]Cl, were investigated to determine their influence on the aggregation and disaggregation of PrP106-126. The steric and aromatic effects of the ligand resulted in enhanced binding affinity. Inhibition was significantly affected by a large ligand. The neurotoxicity of the SH-SY5Y cells induced by PrP106-126 was reduced by the three Au-bpy derivants. However, the disaggregation ability was not in accordance with the results obtained for selected complexes during inhibition, suggesting a different mechanism of interaction between gold complexes and PrP106-126. The key peptide residues contributed to both the inhibition and disaggregation capabilities through the metal coordination and the hydrophobic interaction with the metal complexes. Thus, understanding the aggregation mechanism of the prion peptide would be helpful in designing novel metal-based drugs against amyloid fibril formation.
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Current Use of Domperidone and Co-prescribing of Medications that Increase Its Arrhythmogenic Potential Among Older Adults: A Population-Based Cohort Study in Ontario, Canada.
Drugs Aging
PUBLISHED: 09-18-2014
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Domperidone is commonly used to treat nausea and gastrointestinal disorders. Recent data suggests that it may increase the risk of sudden cardiac death, particularly in older people. Little is known about how it is used in contemporary practice. This study sought to characterize the population of older adults newly dispensed domperidone, describe dosages of domperidone used, and determine the frequency of co-prescribing domperidone with medications that may increase the arrhythmogenic potential of domperidone.
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Dimensionality Reduction for Hyperspectral Data Based on Class-Aware Tensor Neighborhood Graph and Patch Alignment.
IEEE Trans Neural Netw Learn Syst
PUBLISHED: 09-16-2014
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To take full advantage of hyperspectral information, to avoid data redundancy and to address the curse of dimensionality concern, dimensionality reduction (DR) becomes particularly important to analyze hyperspectral data. Exploring the tensor characteristic of hyperspectral data, a DR algorithm based on class-aware tensor neighborhood graph and patch alignment is proposed here. First, hyperspectral data are represented in the tensor form through a window field to keep the spatial information of each pixel. Second, using a tensor distance criterion, a class-aware tensor neighborhood graph containing discriminating information is obtained. In the third step, employing the patch alignment framework extended to the tensor space, we can obtain global optimal spectral-spatial information. Finally, the solution of the tensor subspace is calculated using an iterative method and low-dimensional projection matrixes for hyperspectral data are obtained accordingly. The proposed method effectively explores the spectral and spatial information in hyperspectral data simultaneously. Experimental results on 3 real hyperspectral datasets show that, compared with some popular vector- and tensor-based DR algorithms, the proposed method can yield better performance with less tensor training samples required.
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Fusion of photodynamic therapy and photoactivated chemotherapy: a novel Ru(II) arene complex with dual activities of photobinding and photocleavage toward DNA.
Dalton Trans
PUBLISHED: 09-05-2014
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Transition metal complexes with dual functions of DNA photobinding via coordination and DNA photocleavage via(1)O2 may present potent antitumor activities with high selectivity and a wide anticancer spectrum. We herein report such a complex, [(?(6)-p-cymene)Ru(dpb)(py)](2+) (dpb = 2,3-bis(2-pyridyl)benzoquinoxaline, py = pyridine, 1). The highly delocalized nature of dpb provides 1 with long wavelength-absorbing properties and a long-lived excited state, facilitating (1)O2 generation. Additionally, the bulky nature of dpb leads to a distorted coordination geometry, and allow the (3)MC (metal-centered) state to be more accessible. From this, dissociation of py and dpb may occur, followed by the coordination of the resultant Ru fragment to nucleic bases if DNA is present. The dissociation of dpb can turn on fluorescence of its own, enabling real-time imaging of the photoactivation process. The fascinating properties of 1 and the underlying mechanisms that occur may provide guidelines for developing more efficient metallodrugs with dual potential for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT).
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The effect of amphiphilic polymers on the association, morphology and photophysical properties of hypocrellin coordination polymer/fullerene assemblies.
Photochem. Photobiol. Sci.
PUBLISHED: 08-28-2014
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The yttrium coordination polymer of pyrene modified hypocrellin A (Y(3+)-PyrHA) is synthesized and characterized. The methoxydiglycol malonate modified fullerene can be included in the cavity of Y(3+)-PyrHA in organic solution and buffer solution containing amphiphilic polymers, such as polyvinyl pyrrolidone (PVP), pluronic F127 and P123. The interaction between an amphiphilic polymer and Y(3+)-PyrHA plays an important role in controlling the size and morphology of Y(3+)-PyrHA/fullerene. TEM images of Y(3+)-PyrHA/fullerene in 1% F127 and P123 show nanoparticles in the size range 10-60 nm, while TEM images of Y(3+)-PyrHA/fullerene in 1% PVP display large-scale aggregation. Singlet oxygen is generated by irradiation of the polymer solution of Y(3+)-PyrHA/fullerene in the presence of oxygen. The electron paramagnetic resonance (EPR) spin trapping and 9,10-dimethoxyanthracene-2-sulfonic acid sodium salt (MAS) photooxidation results suggest that in 1% P123 solution Y(3+)-PyrHA/fullerene exhibits a higher singlet oxygen quantum yield than Y(3+)-PyrHA and the corresponding fullerene.
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Decreased oxygen saturation in asymmetrically prominent cortical veins in patients with cerebral ischemic stroke.
Magn Reson Imaging
PUBLISHED: 08-15-2014
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Decreased oxygen saturation in asymmetrically prominent cortical veins (APCV) seen in ischemic stroke has been hypothesized to correlate with an increase of de-oxygenated hemoglobin. Our goal is to quantify magnetic susceptibility to define APCV by establishing a cutoff above which the deoxyhemoglobin levels are considered abnormal. A retrospective study was conducted on 26 patients with acute ischemic stroke in one cerebral hemisphere that exhibited APCV with 30 age- and sex-matched healthy controls. Quantitative susceptibility mapping (QSM) was used to calculate the magnetic susceptibility of the cortical veins. A paired t-test was used to compare the susceptibility of the cortical veins in the left and right hemispheres for healthy controls as well as in the contralateral hemisphere for stroke patients with APCV. The change in oxygen saturation in the APCV relative to the contralateral side was calculated after thresholding the susceptibility using the mean plus two standard deviations of the contralateral side for each individual. The thresholded susceptibility value of the APCVs in the stroke hemisphere was 254±48ppb which was significantly higher (p<0.05) than that in the contralateral hemisphere (123±12ppb) and in healthy controls (125±8ppb). There was a decrease of oxygen saturation in the APCV ranging from 16% to 44% relative to the veins of the contralateral hemisphere. In conclusion, APCV seen in SWI correspond to reduced levels of oxygen saturation and these abnormal veins can be identified using a susceptibility threshold on the QSM data.
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Controllable fabrication of zinc borate hierarchical nanostructure on brucite surface for enhanced mechanical properties and flame retardant behaviors.
ACS Appl Mater Interfaces
PUBLISHED: 05-19-2014
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A novel and efficient halogen-free composite flame retardant (CFR) consisting of a brucite core and a fine zinc borate [Zn6O(OH)(BO3)3] hierarchical nanostructure shell was designed and synthesized via a facile nanoengineering route. It had been demonstrated that this unique hybrid structure possessed a high BET specific surface area (65 m(2)/g) and could significantly enhance the interfacial interaction when mixing with ethylene-vinyl acetate (EVA). This improved the transfer of stress between CFR particles and EVA matrix and increased the viscosity of EVA/EVA blends, which was beneficial for droplet inhibition and char forming. The mechanical properties and flammability behaviors of the EVA/CFR blends had been compared with the EVA/physical mixture (PM, with the given proportion of brucite and Zn6O(OH)(BO3)3). The mechanical properties of EVA/CFR blends, especially the tensile strength (TS), presented a remarkable increase reaching at least a 20% increment. Meanwhile, with the same 45 wt % of fillers, the EVA/CFR formulation could achieve a limiting oxygen index (LOI) value of 33 (37.5 % higher than that of EVA/PM blends) and UL-94 V-0 rating. Moreover, the heat release rate (HRR), peak heat release rate (PHRR), total heat released (THR), smoke production rate (SPR) and mass loss rate (MLR) were considerably reduced, especially PHRR and SPR for EVA/CFR blends were reduced to 32%. According to this study, the design of fine structure might pave the way for the future development of halogen-free flame retardants combining both enhanced mechanical properties and excellent flame retardant behaviors.
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An unexpected role of the monodentate ligand in photocatalytic hydrogen production of the pentadentate ligand-based cobalt complexes.
Chem. Commun. (Camb.)
PUBLISHED: 05-13-2014
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The dissociation of one pyridine of a pentadentate ligand (N4Py) from the Co centre was found to be responsible for the formation of a Co(III) hydride species, an indispensable intermediate for photocatalytic proton reduction.
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In Vitro Photodynamic Inactivation Effects of Ru(II) Complexes on Clinical Methicillin-resistant Staphylococcus aureus Planktonic and Biofilm Cultures.
Photochem. Photobiol.
PUBLISHED: 05-10-2014
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Photosensitizers (PSs) combined with light are able to generate antimicrobial effects. Ru(II) complexes have been recognized as a novel class of PSs. In this study, we investigated the effectiveness of photodynamic inactivation (PDI) mediated by three Ru(II) polypyridine complexes, 1-3, against four isolates of clinical methicillin-resistant Staphylococcus aureus (MRSA-1, MRSA-2, MRSA-3 and MRSA-4). In PDI of a planktonic culture of MRSA-1, compound 3 showed the highest efficacy, likely owing to its advantageous light absorption, (1) O2 quantum yield and bacterial cellular binding. The PDI efficacy of 3 was further evaluated against all other strains and MRSA-1 biofilms. At appropriate PS concentrations, viability reduction of 100% or 96.83% was observed in planktonic or biofilm forms of MRSA, respectively. The mechanisms of action were investigated using negative staining transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). It was demonstrated that PDI of planktonic bacteria was achieved primarily through damage to the cell envelope. Biofilms were eliminated through both the destruction of their structure and inactivation of the individual bacterial cells. In conclusion, Ru(II) complexes, especially 3, are potential candidates for the effective photodynamic control of MRSA infections. This article is protected by copyright. All rights reserved.
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Regulation of aggregation behavior and neurotoxicity of prion neuropeptides by platinum complexes.
Inorg Chem
PUBLISHED: 05-02-2014
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Prion diseases belong to a group of infectious, fatal neurodegenerative disorders. The conformational conversion of a cellular prion protein (PrP(C)) into an abnormal misfolded isoform (PrP(Sc)) is the key event in prion disease pathology. PrP106-126 resembles PrP(Sc) in some physicochemical and biological characteristics, such as apoptosis induction in neurons, fibrillar formation, and mediation of the conversion of native cellular PrP(C) to PrP(Sc). Numerous studies have been conducted to explore the inhibiting methods on the aggregation and neurotoxicity of prion neuropeptide PrP106-126. We showed that PrP106-126 aggregation, as assessed by fluorescence assay and atomic force microscopy, is inhibited by platinum complexes cisplatin, carboplatin, and Pt(bpy)Cl2. ESI-MS and NMR assessments of PrP106-126 and its mutant peptides demonstrate that platinum complexes bind to the peptides in coordination and nonbonded interactions, which rely on the ligand properties and the peptide sequence. In peptides, methionine residue is preferred as a potent binding site over histidine residue for the studied platinum complexes, implying a typical thiophile characteristic of platinum. The neurotoxicity induced by PrP106-126 is better inhibited by Pt(bpy)Cl2 and cisplatin. Furthermore, the ligand configuration contributes to both the binding affinity and the inhibition of peptide aggregation. The pursuit of novel platinum candidates that selectively target prion neuropeptide is noteworthy for medicinal inorganic chemistry and chemical biology.
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Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD.
Eur. Respir. J.
PUBLISHED: 04-17-2014
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Our purpose was to evaluate the association of new benzodiazepine use relative to non-use with adverse clinical respiratory outcomes among older adults with chronic obstructive pulmonary disease (COPD). This was a retrospective population-based cohort study of Ontario, Canada, residents between 2003 and 2010. A validated algorithm was applied to health administrative data to identify adults aged 66 years and older with COPD. Relative risks (RRs) of several clinically important respiratory outcomes were examined within 30 days of incident benzodiazepine use compared with non-use, applying propensity score matching. New benzodiazepine users were at significantly higher risk for outpatient respiratory exacerbations (RR 1.45, 95% CI 1.36-1.54) and emergency room visits for COPD or pneumonia (RR 1.92, 95% CI 1.69-2.18) compared to non-users. Risk of hospitalisation for COPD or pneumonia was also increased in benzodiazepine users, but was nonsignificant (RR 1.09, 95% CI 1.00-1.20). There were no significant differences in intensive care unit admissions between the two groups and all-cause mortality was slightly lower among new versus non-users. Benzodiazepines were associated with increased risk for several serious adverse respiratory outcomes among older adults with COPD. The findings suggest that decisions to use benzodiazepines in older patients with COPD need to consider potential adverse respiratory outcomes.
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Inhibition of human amylin fibril formation by insulin-mimetic vanadium complexes.
Metallomics
PUBLISHED: 04-10-2014
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The toxicity of amyloid-forming proteins can be linked to many degenerative and systemic diseases. Human islet amyloid polypeptide (hIAPP, amylin) has been associated with type II diabetes. Methods for efficient inhibition of amyloid fibril formation are highly clinically important. This study demonstrated the significant inhibitory effects of six vanadium complexes on hIAPP aggregation. Vanadium complexes, such as bis(maltolato)-oxovanadium (BMOV), have been used as insulin-mimetic agents for the treatment of diabetes for many years. Different biophysical methods were applied to investigate the interaction between V complexes and hIAPP. The results indicated that the selected compounds affected the peptide aggregation by different action modes and protected the cells from the cytotoxicity induced by hIAPP. Both the high binding affinity and the ligand spatial effect on inhibiting hIAPP aggregation are significant. Although some of these compounds undergo biotransformation under the conditions of the experiments, and the active species are not identified, it is understood that the effect results from a particular compound and its conversion products. Importantly, our work provided information on the effects of the selected V complexes on hIAPP and demonstrated multiple levels of effects of V complexes against amyloid-related diseases.
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Safety modeling of suburban arterials in Shanghai, China.
Accid Anal Prev
PUBLISHED: 04-07-2014
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As urbanization accelerates in Shanghai, land continues to develop along suburban arterials which results in more access points along the roadways and more congested suburban arterials; all these changes have led to deterioration in traffic safety. In-depth safety analysis is needed to understand the relationship between roadway geometric design, access features, traffic characteristics, and safety. This study examined 161 road segments (each between two adjacent signalized intersections) of eight suburban arterials in Shanghai. Information on signal spacing, geometric design, access features, traffic characteristics, and surrounding area types were collected. The effect of these factors on total crash occurrence was investigated. To account for the hierarchical data structure, hierarchical Bayesian models were developed for total crashes. To identify diverse effects on different crash injury severity, the total crashes were separated into minor injury and severe injury crashes. Bivariate hierarchical Bayesian models were developed for minor injury and severe injury to account for the correlation among different severity levels. The modeling results show that the density of signal spacing along arterials has a significant influence on minor injury, severe injury, and total crash frequencies. The non-uniform signal spacing has a significant impact on the occurrence of minor injury crashes. At the segment-level, higher frequencies of minor injury, severe injury, and total crashes tend to occur for the segments with curves, those with a higher density of access points, those with a higher percentage of heavy vehicles, and those in inner suburban areas. This study is useful for applications such as related engineering safety improvements and making access management policy.
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The effect of multidisciplinary heart failure clinic characteristics on 1-year postdischarge health care costs: a population-based study.
Med Care
PUBLISHED: 02-11-2014
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Although multidisciplinary heart failure (HF) clinics are efficacious, it is not known how patient factors or HF clinic structural indicators and process measures have an impact on the cumulative health care costs.
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Greater mortality risk among patients with delayed follow-up after implantable cardioverter defibrillator procedures.
Can J Cardiol
PUBLISHED: 02-08-2014
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Substantial numbers of deaths occur among implantable cardioverter defibrillator (ICD) recipients. Timely follow-up after ICD implantation might improve patient outcomes. Our objective was to examine follow-up care and outcomes among patients undergoing ICD implantation.
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Proteomic analysis of the interaction of Bifidobacterium longum NCC2705 with the intestine cells Caco-2 and identification of plasminogen receptors.
J Proteomics
PUBLISHED: 01-18-2014
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To identify proteins with a potential role in the interaction of Bifidobacterium longum with intestinal epithelial cells, we profiled the protein response of B. longum NCC2705 following interaction with Caco-2 cells. Thirty-one protein spots, belonging to a total of 23 proteins, which exhibited a change in abundance of at least 3-fold were identified in B. longum NCC2705 following co-culture with Caco-2 cells, and were subsequently identified. Changes in expression were confirmed at the transcriptional level for a selection of these proteins. Enolase (Eno) and elongation factor Tu (EF-Tu) were amongst the proteins that showed the most prominent increase in abundance. Interaction of these proteins with plasminogen (Plg) was analyzed by Plg overlay assays, glutathione S-transferase (GST)-pull down, and western blot analysis. The results suggested that EF-Tu and Eno serve as surface receptors for B. longum NCC2705 binding to human plasminogen. Purified GST-EF-Tu and GST-Eno inhibited adhesion of B. longum NCC2705 to Caco-2 cells. Collectively, our data suggest that Eno and EF-Tu moonlight as adhesions, and are possibly involved in the protective role played by B. longum NCC2705 in defense against enteric pathogens. Biological significance The interaction of bifidobacteria with the human host plasminogen/plasmin system confirms the existence of a new component in the molecular cross-talk between bacteria and the host. Our study analyzed proteins EF-Tu and Eno with Plg binding activity, and they can inhibit adhesion of B. longum NCC2705 to Caco-2 cells, suggesting their role in the bacterial adherent to the enterocyte surface.
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The locust genome provides insight into swarm formation and long-distance flight.
Nat Commun
PUBLISHED: 01-16-2014
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Locusts are one of the world's most destructive agricultural pests and represent a useful model system in entomology. Here we present a draft 6.5?Gb genome sequence of Locusta migratoria, which is the largest animal genome sequenced so far. Our findings indicate that the large genome size of L. migratoria is likely to be because of transposable element proliferation combined with slow rates of loss for these elements. Methylome and transcriptome analyses reveal complex regulatory mechanisms involved in microtubule dynamic-mediated synapse plasticity during phase change. We find significant expansion of gene families associated with energy consumption and detoxification, consistent with long-distance flight capacity and phytophagy. We report hundreds of potential insecticide target genes, including cys-loop ligand-gated ion channels, G-protein-coupled receptors and lethal genes. The L. migratoria genome sequence offers new insights into the biology and sustainable management of this pest species, and will promote its wide use as a model system.
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Demographic characteristics and healthcare use of centenarians: a population-based cohort study.
J Am Geriatr Soc
PUBLISHED: 01-02-2014
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To better understand how centenarians use the healthcare system as an important step toward improving their service delivery.
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Association of Heart Rate at Hospital Discharge with Mortality and Hospitalizations in Patients with Heart Failure.
Circ Heart Fail
PUBLISHED: 12-02-2013
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-Heart failure (HF) is associated with a high burden of morbidity and mortality. Hospital discharge is an opportunity for identification of modifiable prognostic factors in the transition to chronic HF.
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Tandem synthesis of 3-allyl-chromones from alkynones and allylic alcohols under metal-free conditions.
Chem. Commun. (Camb.)
PUBLISHED: 11-26-2013
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A novel and efficient approach to 3-allyl-chromones from alkynones and allylic alcohols via a tandem Michael addition-Claisen rearrangement-O-arylation reaction has been developed. Diversely structural 3-allyl-chromones were afforded in up to 93% yield for 24 examples. This synthetic strategy is regiospecific, highly efficient, environment friendly and metal-free.
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Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach.
BMC Gastroenterol
PUBLISHED: 09-06-2013
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Assessment and characterization of human colon microbiota is now a major research area in human diseases, including in patients with hepatitis B liver cirrhosis (HBLC).
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A metal-free multicomponent cascade reaction for the regiospecific synthesis of 1,5-disubstituted 1,2,3-triazoles.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-26-2013
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About specifics: A method for the regiospecific synthesis of the title compounds through an unprecedented Michael addition/deacylative diazo transfer/cyclization sequence has been established. The simple and practical method can be used for the modification of primary amines including chiral ?-amines. The process involves the formation three covalent bonds and the cleavage of two covalent bonds (see scheme, Ts=4-toluenesulfonyl).
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Management of neuropsychiatric symptoms in long-term care residents with Parkinsons disease: a retrospective cohort study.
Drugs Aging
PUBLISHED: 07-09-2013
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The management of neuropsychiatric symptoms, including psychosis, in Parkinsons Disease (PD) is complicated by the fact that treatment with antipsychotics can worsen the movement disorder, which may necessitate changes to antiparkinsonian medications.
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Administrative hospitalization database validation of cardiac procedure codes.
Med Care
PUBLISHED: 05-03-2013
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Although cardiac procedures are commonly used to treat cardiovascular disease, they are costly. Administrative data sources could be used to track cardiac procedures, but sources of such data have not been validated against clinical registries.
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Gold complexes inhibit the aggregation of prion neuropeptides.
J. Biol. Inorg. Chem.
PUBLISHED: 03-19-2013
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Prion diseases are characterized by conformational conversion of prion protein from a normal cellular form to an abnormal scrapie isoform (PrP(Sc)). PrP106-126 is a prion neuropeptide and an accepted model used to study the characteristics of PrP(Sc) because such a model has biological and physiochemical properties similar to those of PrP(Sc). Some metal complexes have a strong binding affinity for PrP106-126 and a good inhibitory effect against amyloid fibril formation. However, the effects of the metal ligand configuration on peptide binding and aggregation are not well known. To investigate interaction and peptide aggregation between prion neuropeptides and two gold complexes with different ligand configurations ([Au(bpy)Cl2]PF6 and [Au(dien)Cl]Cl2, where bpy is 2,2-bipyridine and dien is diethylenetriamine), six prion peptides with either a His111-mutated or a Met109/112-mutated residue were used in this study. The selection of the mutant was based on the corresponding neuropeptide from other species. The results showed that the aromatic gold complex [Au(bpy)Cl2]PF6 exhibits better binding affinity and a better inhibitory effect against peptide aggregation than the tridentate complex [Au(dien)Cl]Cl2. For the sequence-specific PrP106-126 and its mutants, His111 plays the most important role in peptide aggregation and binding affinity. Furthermore, Met112 has a greater effect on the binding affinity than Met109. Compared with the mutated short 14 amino acid peptides, the hydrophobic region of PrP106-126 contributes to both binding affinity and self-aggregation behavior. This work will help to understand and develop potential metallodrugs against amyloid disorder.
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Inhibition of human prion neuropeptide PrP106-126 aggregation by hexacoordinated ruthenium complexes.
J. Inorg. Biochem.
PUBLISHED: 03-08-2013
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Prion disease is a neurodegenerative disorder that can occur among humans and other animals. The aberrant isoform of prion protein PrP(Sc) has been identified as the infectious agent. The neuropeptide PrP106-126 has been widely used as a suitable model to study the biological and physiochemical properties of PrP(Sc). PrP106-126 shares several physicochemical and biological properties with PrP(Sc), including cellular toxicity, fibrillogenesis, and membrane-binding affinity. Ruthenium complexes are commonly employed in anti-cancer studies due to their low cellular toxicity. In this study, six hexacoordinated ruthenium complexes with different molecular configurations were used to investigate their effects on PrP106-126 aggregation inhibition. Results revealed that the interaction between the complexes and the peptide included metal coordination and hydrophobic interaction mainly. Those complexes with aromatic structure displayed better inhibitory effects, although they only had a common binding affinity to PrP106-126. This study provided better understanding on the interaction of metal complexes with PrP106-126 and paved the way for potential Ru-based metallodrugs against prion diseases.
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A ruthenium(II) arene complex showing emission enhancement and photocleavage activity towards DNA from singlet and triplet excited states respectively.
Dalton Trans
PUBLISHED: 03-06-2013
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The emission enhancement behavior and photocleavage activity of a ruthenium(II) arene complex, [(?(6)-p-cymene)Ru(dppn)(py)](2+) (1) (dppn = 4,5,9,16-tetraaza-dibenzo[a,c]naphthacene, py = pyridine), towards DNA were compared with [(?(6)-p-cymene)Ru(bpy)(py)](2+) (2), [Ru(bpy)2(dppz)](2+) (3) and [Ru(bpy)2(dppn)](2+) (4) (bpy = 2,2-bipyridine, dppz = dipyrido-[3,2-a:2,3-c]phenazine). It was found that 1 emits fluorescence from the dppn-based ligand-centered (LC) singlet excited state and generates singlet oxygen ((1)O2) from the dppn-based LC triplet excited state. As a result, 1 displays emission enhancement behavior and photocleavage activity towards DNA simultaneously. In contrast, 3 is the most classical DNA light switch but shows poor DNA photocleavage activity, while 4 is an efficient DNA photocleaver but cannot report DNA binding by luminescence enhancement. An increased cytotoxicity against human lung carcinoma cells A549 by about 10-fold was also observed for 1 upon visible light activation. These intriguing properties result from the unique combination of the Ru(II) arene and dppn subunits.
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Self-assembly of anionic porphyrins and alkaline or alkaline earth metal ions mediated by cucurbit[7,8]uril.
Chemphyschem
PUBLISHED: 02-11-2013
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Nanoscaled coordination polymers based on biologically prevalent ions have potential applications in drug delivery and biomedical imaging. Herein, coordination polymer nanoparticles of anionic porphyrins, including meso-tetra(4-carboxyphenyl)-porphyrin (H2 TCPP(4-)) and meso-tetra(4-sulfonatophenyl)-porphyrin (H2 TPPS(4-)), and alkaline or alkaline earth metal cations, such as K(+) and Ca(2+), were constructed in aqueous solution in the presence of cucurbit[7]uril (CB7) or cucurbit[8]uril (CB8). UV/Vis absorption and fluorescence spectroscopy, dynamic light scattering (DLS), scanning electron spectroscopy (SEM), and atomic force microscopy (AFM) were applied to explore the assembly and particle formation of porphyrin anions and metal cations mediated by CBn. The particle size depends on the kinds of CBn and metal cations and their concentrations. The uptake of H2 TPPS(4-) particles by tumor cells (A549 cells) was found to be more efficient than H2 TPPS(4-) at 37?°C, showing the application potential of such assembled particles in biology and medicine.
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Benzodiazepine use among older adults with chronic obstructive pulmonary disease: a population-based cohort study.
Drugs Aging
PUBLISHED: 02-02-2013
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Patients with chronic obstructive pulmonary disease (COPD) may receive benzodiazepines for a variety of reasons, including as treatment for insomnia, as treatment for depression and anxiety, and to help relieve refractory dyspnoea. However, benzodiazepines have been linked to adverse physiological respiratory outcomes in individuals with COPD. The potential adverse respiratory effects of benzodiazepines in COPD may also be heightened in older adults given their altered pharmacokinetics that increase benzodiazepine half-life. There is minimal information on the scope and nature of benzodiazepine use in the older adult COPD population.
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Validity of a novel arthroscopic test to diagnose posterolateral rotational instability of the knee joint: the lateral gutter drive-through test.
Arthroscopy
PUBLISHED: 02-01-2013
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The purpose of this study was to assess the validity of a newly developed arthroscopic test, termed the lateral gutter drive-through (LGDT) test, to diagnose posterolateral rotational instability (PLRI) of the knee joint.
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Investigation of road network features and safety performance.
Accid Anal Prev
PUBLISHED: 01-13-2013
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The analysis of road network designs can provide useful information to transportation planners as they seek to improve the safety of road networks. The objectives of this study were to compare and define the effective road network indices and to analyze the relationship between road network structure and traffic safety at the level of the Traffic Analysis Zone (TAZ). One problem in comparing different road networks is establishing criteria that can be used to scale networks in terms of their structures. Based on data from Orange and Hillsborough Counties in Florida, road network structural properties within TAZs were scaled using 3 indices: Closeness Centrality, Betweenness Centrality, and Meshedness Coefficient. The Meshedness Coefficient performed best in capturing the structural features of the road network. Bayesian Conditional Autoregressive (CAR) models were developed to assess the safety of various network configurations as measured by total crashes, crashes on state roads, and crashes on local roads. The models results showed that crash frequencies on local roads were closely related to factors within the TAZs (e.g., zonal network structure, TAZ population), while crash frequencies on state roads were closely related to the road and traffic features of state roads. For the safety effects of different networks, the Grid type was associated with the highest frequency of crashes, followed by the Mixed type, the Loops & Lollipops type, and the Sparse type. This study shows that it is possible to develop a quantitative scale for structural properties of a road network, and to use that scale to calculate the relationships between network structural properties and safety.
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Impact of Hfq on global gene expression and intracellular survival in Brucella melitensis.
PLoS ONE
PUBLISHED: 01-01-2013
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Brucella melitensis is a facultative intracellular bacterium that replicates within macrophages. The ability of brucellae to survive and multiply in the hostile environment of host macrophages is essential to its virulence. The RNA-binding protein Hfq is a global regulator that is involved in stress resistance and pathogenicity. Here we demonstrate that Hfq is essential for stress adaptation and intracellular survival in B. melitensis. A B. melitensis hfq deletion mutant exhibits reduced survival under environmental stresses and is attenuated in cultured macrophages and mice. Microarray-based transcriptome analyses revealed that 359 genes involved in numerous cellular processes were dysregulated in the hfq mutant. From these same samples the proteins were also prepared for proteomic analysis to directly identify Hfq-regulated proteins. Fifty-five proteins with significantly affected expression were identified in the hfq mutant. Our results demonstrate that Hfq regulates many genes and/or proteins involved in metabolism, virulence, and stress responses, including those potentially involved in the adaptation of Brucella to the oxidative, acid, heat stress, and antibacterial peptides encountered within the host. The dysregulation of such genes and/or proteins could contribute to the attenuated hfq mutant phenotype. These findings highlight the involvement of Hfq as a key regulator of Brucella gene expression and facilitate our understanding of the role of Hfq in environmental stress adaptation and intracellular survival of B. melitensis.
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Fructose uptake in Bifidobacterium longum NCC2705 is mediated by an ATP-binding cassette transporter.
J. Biol. Chem.
PUBLISHED: 11-18-2011
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Recently, a putative ATP-binding cassette (ABC) transport system was identified in Bifidobacterium longum NCC2705 that is highly up-regulated during growth on fructose as the sole carbon source. Cloning and expression of the corresponding ORFs (bl0033-0036) result in efficient fructose uptake by bacteria. Sequence analysis reveals high similarity to typical ABC transport systems and suggests that these genes are organized as an operon. Expression of FruE is induced by fructose, ribose, or xylose and is able to bind these sugars with fructose as the preferred substrate. Our data suggest that BL0033-0036 constitute a high affinity fructose-specific ABC transporter of B. longum NCC2705. We thus suggest to rename the coding genes to fruEKFG and the corresponding proteins to FruE (sugar-binding protein), FruK (ATPase subunit), FruF, and FruG (membrane permeases). Furthermore, protein-protein interactions between the components of the transporter complex were determined by GST pulldown and Western blot analysis. This revealed interactions between the membrane subunits FruF and FruG with FruE, which in vivo is located on the external side of the membrane, and with the cytoplasmatic ATPase FruK. This is in line with the proposed model for bacterial ABC sugar transporters.
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[Reconstruction of medial patellofemoral ligament for recurrent patellar dislocation].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 09-20-2011
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To investigate the procedure and effectiveness of medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent patellar dislocation. METHODS; Between June 2005 and September 2007, 29 patients with recurrent patellar dislocation underwent MPFL reconstruction with allograft semitendinosus or allograft anterior tibialis tendon. There were 6 males and 23 females with an average age of 20.3 years (range, 13-45 years). The patients suffered from 2-10 times patellar dislocation preoperatively. The average time between last dislocation and surgery was 43.9 months (range, 1-144 months). CT scan was performed to measure the tibial tuberosity-trochlear groove distance (TT-TG). The femoral tunnel was made at the origin of MPFL insertion, just inferior to the medial epicondyle. The double L-shape patellar tunnels were made on the medial rim of patella with 4.5 mm in diameter. The loop side of the graft was fixed with a bioabsorbable interference screw in the femoral tunnel both ends of the graft. For the TT-TG was more than 20 mm, a modified Elmslie-Trillat osteotomy was performed to correct the distal alignment of patella. The arthroscopic examination was also performed for loose body and lateral retinacular release.
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Enantioselective degradation of tebuconazole in cabbage, cucumber, and soils.
Chirality
PUBLISHED: 08-10-2011
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The enantioselective degradation of tebuconazole has been investigated to elucidate the behaviors in agricultural soils, cabbage, and cucumber fruit. Rac-tebuconazole was fortified into three types of agricultural soils and sprayed foliage of cabbage and cucumber, respectively. The degradation kinetics, enantiomer fraction and enantiomeric selectivity were determined by reverse-phase high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) on a Lux amylose-2 chiral column. The process of the degradation of tebuconazole enantiomers followed first-order kinetic in the test soils and vegetables. It has been shown that the degradation of tebuconazole was enantioselective. The results indicated that the (+)-S-tebuconazole showed a faster degradation in cabbage, while the (-)-R-tebuconazole dissipated faster than (+)-S-form in cucumber fruit and the test soils.
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Host-guest interaction of Hoechst 34580 and Cucurbit[7]uril.
Chemphyschem
PUBLISHED: 06-29-2011
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To track nuclear dynamic processes by fluorescence imaging, nuclear stains should be highly fluorescent, resistant to photobleaching, and inert to nuclear processes. The nuclear stains of the Hoechst family, such as Hoechst 34580, show bright fluorescence only on groove binding to DNA, and therefore may interfere with visualization of nuclear dynamic processes induced by other stimuli. We study host-guest interactions between Hoechst 34580 and Cucurbit[7]uril (CB7) in aqueous solutions. The formation of CB7-Hoechst 34580 inclusion complexes with stoichiometry of 2:1 in water and 1:1 in phosphate-buffered saline (PBS) solution (pH 7.0) is confirmed by (1)H NMR, absorption spectra, fluorescence spectra, MALDI-TOF MS, and molecular modeling. Compared to Hoechst 34580, the inclusion complex exhibits redshifted absorption, intensified fluorescence, improved photostability, weakened DNA binding affinity, comparable ability to penetrate cell nuclei, and better nuclear-staining capability, and thus a new avenue for the application of cucurbituril in fluorescence imaging is opened.
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Conversion of intratumoral regulatory T cells by human gastric cancer cells is dependent on transforming growth factor-?1.
J Surg Oncol
PUBLISHED: 05-31-2011
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Regulatory T cells (Treg) inhibits immune responses mediated by T cells. This study aimed to investigate whether Treg are accumulated in human gastric cancer tissue and the mechanism of Treg induction by gastric cancer cells.
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Palladium complexes affect the aggregation of human prion protein PrP106-126.
Inorg Chem
PUBLISHED: 04-19-2011
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Many neurodegenerative disorders are induced by protein conformational change. Prion diseases are characterized by protein conformational conversion from a normal cellular form (PrP(C)) to an abnormal scrapie isoform (PrP(Sc)). PrP106-126 is an accepted model for studying the characteristics of PrP(Sc) because they share many biological and physiochemical properties. To understand how metal complexes affect the property of the prion peptide, the present work investigated interactions between Pd complexes and PrP106-126 based on our previous research using Pt and Au complexes to target the peptide. The selected compounds (Pd(phen)Cl(2), Pd(bipy)Cl(2), and Pd(en)Cl(2)) showed strong binding affinity to PrP106-126 and affected the conformation and aggregation of this active peptide in a different binding mode. Our results indicate that it may be the metal ligand-induced spatial effect rather the binding affinity that contributes to better inhibition on peptide aggregation. This finding would prove valuable in helping design and develop novel metallodrugs against prion diseases.
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Validity criterion for the Born approximation convergence in microscopy imaging: comment.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 04-12-2011
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A recent paper [J. Opt. Soc. Am. A26, 1147 (2009)] proposed a new criterion to identify the validity of the Born approximation. In this paper, we present our doubts on the mathematical basis and the applicability of this criterion.
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Photodynamic inactivation of Escherichia coli by Ru(II) complexes.
Photochem. Photobiol. Sci.
PUBLISHED: 03-29-2011
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[Ru(II)(bpy)(2)(dppn)](2+) (bpy = 2,2-bipyridine, dppn = 4,5,9,16-tetraazadibenzo[a,c]naphthacene) was found to be able to photoinactivate Gram-negative Escherichia coli efficiently, showing the potential of transition-metal complexes as photosensitizers in the field of photodynamic antimicrobial chemotherapy (PACT).
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Cardiovascular outcomes are predicted by exercise-stress myocardial perfusion imaging: Impact on death, myocardial infarction, and coronary revascularization procedures.
Am. Heart J.
PUBLISHED: 01-31-2011
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The aim of this study was to determine the impact of myocardial perfusion imaging (MPI) on the outcomes of death, myocardial infarction (MI), and late coronary revascularization procedures.
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Proteomics analysis of Bifidobacterium longum NCC2705 growing on glucose, fructose, mannose, xylose, ribose, and galactose.
Proteomics
PUBLISHED: 01-21-2011
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To investigate the molecular mechanisms underlying carbohydrate uptake and connected metabolic pathways of Bifidobacterium longum NCC2705, the proteomic profiles of bacteria grown on different carbon sources including glucose, fructose, mannose, xylose, ribose, and galactose were analyzed. Our results show that all sugars tested were catabolized via the bifid shunt. Sixty-eight proteins that exhibited changes in abundance of threefold or greater were identified by MS. A striking observation was the differential expression of proteins related to the pyruvate metabolism. Further analysis of acetic acid and lactic acid in the culture supernatants by HPLC at the end of fermentation showed that more lactic acid was produced during growth on fructose, ribose, xylose, galactose and more acetic acid was produced during the fermentation of glucose and mannose. Growth experiments revealed that B. longum NCC2705 preferentially used fructose, ribose, xylose, and galactose with higher growth rates over glucose and mannose. Furthermore, five proteins (GroEL, Eno, Tal, Pgm, and BL0033) exhibited clear phosphorylation modifications at serine and/or tyrosine residues. BL0033, a component of an ATP-binding cassette (ABC) transporter, was significantly more abundant in bacteria grown on fructose and, to a lesser extent, ribose and xylose. RT-PCR analysis revealed that all genes of the ABC transporter are induced in the presence of these sugars suggesting that BL0033, BL0034, BL0035, and BL0036 constitute an ABC transporter with fructose as preferred substrate.
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Cost-effectiveness of specialized multidisciplinary heart failure clinics in Ontario, Canada.
Value Health
PUBLISHED: 11-23-2010
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Specialized multidisciplinary clinics have been shown to reduce mortality in heart failure (HF). Our objective was to evaluate the cost-effectiveness of this model of care delivery.
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Greatly enhanced binding of a cationic porphyrin towards bovine serum albumin by cucurbit[8]uril.
Phys Chem Chem Phys
PUBLISHED: 09-08-2010
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Binding affinity towards serum albumin and intracellular proteins is of importance for a photodynamic therapy (PDT) sensitizer to selectively localize in tumours and efficiently induce cell death. In this paper, it was found that cucurbit[8]uril (CB8) can greatly improve the binding affinity of 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP), a promising PDT photosensitizer, towards bovine serum albumin (BSA). Absorption, fluorescence emission, (1)H NMR, dynamic light scattering, atomic force microscope, as well as protein photocleavage measurements suggest that the binding enhancement originates from the formation of a ternary complex of CB8·TMPyP·tryptophan residues. This finding opens up a new approach for the development of more efficient PDT agents.
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Acidic and basic properties and buffer capacity of airborne particulate matter in an urban area of Beijing.
Environ Monit Assess
PUBLISHED: 06-15-2010
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Particles with aerodynamic diameters <10 microm (PM(10)) and particles with aerodynamic diameters <2.5 microm (PM(2.5)) were sampled during summer 2006 in Beijing and mass concentrations, water-soluble ionic compounds concentrations, and acidic buffer capacity were analyzed. Results show that the mass concentration ranges of PM(10) and PM(2.5) were from 56.4 to 226.6 microg/m(3) and from 31.3 to 200.7 microg/m(3) during sampling days, respectively. Concentrations of F(-), Cl(?-), NO3(-), NO2(-), SO4(2-), Ac(-), Ca(2+), Na(+), K(+), Mg(2+), and NH4(+) in particles were analyzed by ion chromatography. Microtitration was adapted to determine the acidic-basic property and the change of the buffering systems in different pH of the aqueous solution in which the PM is suspended. The major alkalinity and buffer capacity of particles were analyzed and calculated. The average carbonate buffer capacity was 0.3 mmol/g in PM(2.5) and 0.7 mmol/g in PM(10). The average acetic acid buffer capacity was 0.1 mmol/g in PM(2.5) and 0.3 mmol/g in PM(10). Carbonate and acetic acid are the main species for the buffer capacity in the particle phase. The average mass of carbonate was 71.0 mg/g in PM(10) and 46.7 mg/g in PM(2.5). The average mass of acetic acid was 11.2 mg/g in PM(2.5) and 20.0 mg/g in PM(10).
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Provider volumes and early outcomes of primary total joint replacement in Ontario.
Can J Surg
PUBLISHED: 05-29-2010
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A relation between provider volume and outcome of total joint replacement (TJR) has not been demonstrated in Canada. Given the recent increase in TJR, changing patient characteristics and small sizes of previous Ontario studies, we reassessed whether adverse outcomes of TJR are related to hospital and surgeon procedure volumes.
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Confounders and intermediaries in case-control study designs: a strategy for distinguishing between the two when measured using the same variable.
Pharmacoepidemiol Drug Saf
PUBLISHED: 04-23-2010
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An intermediary falls within the exposure-outcome pathway and is distinct from a confounder. In case-control studies, it may be difficult to discern between the two when both are measured by the same variable. Using data from a study on the effects of antipsychotic initiation on risk of death among older adults, where hospital use is both a confounder and intermediary, we illustrate the bias introduced when this distinction is overlooked and propose a modified exposure classification strategy to mitigate this.
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pH-responsive silica nanoparticles for controllable 1O2 generation.
Nanotechnology
PUBLISHED: 02-22-2010
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pH-responsive (1)O(2) photosensitizing systems may serve as selective photodynamic therapy (PDT) agents by targeting the acidic interstitial fluid of many kinds of tumors. In this work, we present a pH-responsive nanoparticle-based platform for controllable (1)O(2) generation, in which a hydrophobic (1)O(2) photosensitizer (meso-tetraphenylporphyrin, TPP) and a pH indicator (Bromocresol Purple, BCP, or Bromothymol Blue, BTB) are simultaneously encapsulated in organically modified silica nanoparticles (OSNP). In basic conditions, the pH indicator absorbs light competitively and thus restricts sensitizer excitation. In acidic solution, the blue shifted absorption of the pH indicator allows the efficient excitation of the sensitizer. The pH indicator serves as an inner filter to modulate effectively the excitation of the sensitizer and thus the (1)O(2) generation efficiency.
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Proteomic analysis of the Enterococcus faecalis V583 strain and clinical isolate V309 under vancomycin treatment.
J. Proteome Res.
PUBLISHED: 02-05-2010
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To understand the molecular mechanisms of bacteria resistance to glycopeptides, we obtained proteomic profiles of vancomycin-resistant Enterococcus faecalis V583 (reference strain) and V309 (clinical isolate) passaged with and without the drug. The specificity and reversibility of vancomycin resistance genes induced in V583 and V309 were further studied over time. By semiquantitative RT-PCR of vancomycin-treated versus untreated samples of both strains, 28 (V583) or 20 (V309) up-regulated proteins, 8 (V583) or 6 (V309) down-regulated proteins, and 1 (V583) or 4 (V309) proteins with mobility changes in 2-DE gel analysis were identified. Some of these proteins have known vancomycin resistance functions or are related to virulent factors, stress, metabolism, translation, and conjunction, which would help Enterococcus survive under drug selection. Vancomycin induced specifically and reversibly VanA, VanX, VanB, and VanXB. Notably, 6 proteins (Pgm, Ldh, Gap-2, RpsB, EF2076, and sex pheromone cAD1 precursor lipoprotein) exhibited clear post-translational modifications. Vancomycin induced phosphorylation of Ser/Thr in Ldh, Gap-2, and sex pheromone cAD1 precursor lipoprotein (EF3256), newly identified here as enterococcal phosphoproteins. Our data suggest that phosphorylated EF3256 is normally active in E. faecelis, whereas EF3256-P together with oppA-like protein may play a key role in the regulation of pheromone and transmission of conjugation plasmids.
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Association of blood pressure at hospital discharge with mortality in patients diagnosed with heart failure.
Circ Heart Fail
PUBLISHED: 09-24-2009
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Higher blood pressure in acute heart failure has been associated with improved survival; however, the relationship between blood pressure and survival in stabilized patients at hospital discharge has not been established.
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Short- and long-term risk stratification using a next-generation, high-sensitivity research cardiac troponin I (hs-cTnI) assay in an emergency department chest pain population.
Clin. Chem.
PUBLISHED: 08-13-2009
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The next-generation, high-sensitivity cardiac troponin assays can measure quantifiable concentrations of cTn in a majority of individuals, but there are few studies assessing these assays for risk stratification. The present study was undertaken to determine if a research hs-cTnI assay can be useful for predicting death/myocardial infarction (MI), both short- and long-term, in an emergency department acute coronary syndrome (ACS) population.
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Mitochondria-targeting properties and photodynamic activities of porphyrin derivatives bearing cationic pendant.
J. Photochem. Photobiol. B, Biol.
PUBLISHED: 06-24-2009
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Four meso-tetraphenylporphyrin derivatives bearing either triphenylphosphonium ion-(P1 and P2) or triethylammonium ion-(P3 and P4) terminated alkoxy group at either para-(P1 and P3) or meta-(P2 and P4) position of one meso-phenyl group were designed and synthesized. P1-P4 show similar absorption and fluorescence emission spectra and (1)O(2) quantum yields. The more lipophilic nature of triphenylphosphonium ion over triethylammonium ion renders P1 and P2 higher octanol/water partition coefficients than P3 and P4. Confocal fluorescence microscopy proved that P1-P4 are all mitochondria-targeting. MTT assay showed that P1-P4 presented significant phototoxicity at the concentrations that dark toxicity is negligible towards human breast cancer cell line MCF-7 cells, displaying their application potential in PDT.
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Validation of a health administrative data algorithm for assessing the epidemiology of diabetes in Canadian children.
Pediatr Diabetes
PUBLISHED: 06-05-2009
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To validate a case definition of pediatric diabetes using administrative health data and describe trends in incidence and prevalence over time in Ontario, Canada.
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Modeling signalized intersection safety with corridor-level spatial correlations.
Accid Anal Prev
PUBLISHED: 02-23-2009
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Intersections in close spatial proximity along a corridor should be considered as correlated due to interacted traffic flows as well as similar road design and environmental characteristics. It is critical to incorporate this spatial correlation for assessing the true safety impacts of risk factors. In this paper, several Bayesian models were developed to model the crash data from 170 signalized intersections in the state of Florida. The safety impacts of risk factors such as geometric design features, traffic control, and traffic flow characteristics were evaluated. The Poisson and Negative Binomial Bayesian models with non-informative priors were fitted but the focus is to incorporate spatial correlations among intersections. Two alternative models were proposed to capture this correlation: (1) a mixed effect model in which the corridor-level correlation is incorporated through a corridor-specific random effect and (2) a conditional autoregressive model in which the magnitude of correlations is determined by spatial distances among intersections. The models were compared using the Deviance Information Criterion. The results indicate that the Poisson spatial model provides the best model fitting. Analysis of the posterior distributions of model parameters indicated that the size of intersection, the traffic conditions by turning movement, and the coordination of signal phase have significant impacts on intersection safety.
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PAPP-A as a marker of increased long-term risk in patients with chest pain.
Clin. Biochem.
PUBLISHED: 02-02-2009
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Long-term risk stratification in patients presenting with acute coronary syndromes (ACS) is possible by measuring cardiac troponin (cTn). The present study examined whether PAPP-A measured in an emergency department (ED) chest pain population in association with conventional and novel high sensitivity cTn (hs-cTnI) assays can predict long-term mortality.
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Ruthenium complexes as novel inhibitors of human islet amyloid polypeptide fibril formation.
Metallomics
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Human islet amyloid polypeptide (hIAPP) can be linked to the pathology of type II diabetes. In this study, aromatic ring-containing Ru complexes were found to effectively inhibit the fibril formation of hIAPP and promote the disaggregation of formed fibrils by remarkably changing the ?-sheet components.
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Combined use of spinal cord-mimicking partition type scaffold architecture and neurotrophin-3 for surgical repair of completely transected spinal cord in rats.
J Biomater Sci Polym Ed
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A body of evidence has suggested that tissue-engineered nerve grafts hold promise for the surgical repair of spinal cord injuries. In this study, a novel nerve graft was prepared to be implantated into a 5?mm gap which was caused by a complete transection of the rat spinal cord. The graft was featured by incorporation of neurotrophin-3 into a chitosan-based tube scaffold with a spinal cord-mimicking, partition-type architecture, which was prepared based on the morphometric insights of normal spinal cord anatomy. A set of behavioral, functional, and histological examinations were carried out to evaluate the repair. Results from Basso, Beattie, and Bresnahan tests, motor evoked potential measurements, anterograde tracing, and histological analyses suggested that the combined application of chitosan as the scaffold biomaterial, a spinal cord-mimicking partition-type as the scaffold architecture, and neurotrophin-3 (NT-3) as the bioactive component might probably create synergetic promotion on spinal cord regeneration. This composite nerve graft yielded significantly better results in axonal regeneration and function restoration as compared to its scaffold alone or other types of hollow tube scaffold alone.
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A population-based study to evaluate the effectiveness of multidisciplinary heart failure clinics and identify important service components.
Circ Heart Fail
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Multidisciplinary heart failure (HF) clinics are efficacious in clinical trials. Our objectives were to compare real-world outcomes of patients with HF treated in HF clinics versus usual therapy and identify HF clinic features associated with improved outcomes.
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Atypical antipsychotic use and parkinsonism in dementia: effects of drug, dose, and sex.
Am J Geriatr Pharmacother
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Differences between atypical antipsychotics in their potential to cause parkinsonism and risk factors for antipsychotic-induced parkinsonism are not well established. There is a particular paucity of information on this in real-world use of these drugs, outside of clinical trial settings.
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Economic analysis of Heart and Stroke Foundation of Ontarios Hypertension Management Initiative.
Clinicoecon Outcomes Res
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Hypertension is suboptimally treated in primary care settings. We evaluated the cost-effectiveness of the Heart and Stroke Foundation of Ontarios Hypertension Management Initiative (HMI), an interdisciplinary, evidence-informed chronic disease management model for primary care that focuses on improving blood pressure management and control by primary care providers and patients according to clinical best practice guidelines.
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Corridor-level signalized intersection safety analysis in Shanghai, China using Bayesian hierarchical models.
Accid Anal Prev
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Most traffic crashes in Chinese cities occur at signalized intersections. Research on the intersection safety problem in China is still in its early stage. The recent development of an advanced traffic information system in Shanghai enables in-depth intersection safety analyses using road design, traffic operation, and crash data. In Shanghai, the road network density is relatively high and the distance between signalized intersections is small, averaging about 200m. Adjacent signalized intersections located along the same corridor share similar traffic flows, and signals are usually coordinated. Therefore, when studying intersection safety in Shanghai, it is essential to account for intersection correlations within corridors. In this study, data for 195 signalized intersections along 22 corridors in the urban areas of Shanghai were collected. Mean speeds and speed variances of corridors were acquired from taxis equipped with Global Positioning Systems (GPS). Bayesian hierarchical models were applied to identify crash risk factors at both the intersection and the corridor levels. Results showed that intersections along corridors with lower mean speeds were associated with fewer crashes than those with higher speeds, and those intersections along two-way roads, under elevated roads, and in close proximity to each other, tended to have higher crash frequencies.
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Rapid detection of Trichinella spiralis larvae in muscles by loop-mediated isothermal amplification.
Int. J. Parasitol.
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Trichinella spiralis is a tissue-dwelling nematode parasite. A loop-mediated isothermal amplification (LAMP) assay was developed and validated for the sensitive and rapid detection of T. spiralis larvae in muscle samples. Sixteen sets of primers were designed to recognise distinct sequences of a conserved gene, a 1.6kb repetitive element of the Trichinella genome. One set of primers was selected as the most appropriate for rapid detection. The specificity and sensitivity of the primers in LAMP reactions for T. spiralis larvae and muscle samples of mice infected with T. spiralis were determined. Another 10 heterologous parasites were selected for specificity assays. The results showed that target DNA was amplified and visualised by monitoring turbidity and adding calcein detection methods within 70min at an isothermal temperature of 63°C. The sensitivity of LAMP with the detection limit of 362fg/?l was >10 times higher than that for PCR. The designed primers had a good specificity. No cross-reactivity was found with the DNA of any other parasites. The assay was able to detect T. spiralis in all mouse muscle samples infected with 10 T. spiralis larvae on day 20 p.i. We believe this is the first report regarding the application of the LAMP assay for detection of T. spiralis larvae in muscle samples from experimentally infected mice. This method demonstrates a potentially valuable means for the direct detection of T. spiralis larvae in meat inspection.
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Shigella flexneri T3SS effector IpaH4.5 modulates the host inflammatory response via interaction with NF-?B p65 protein.
Cell. Microbiol.
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Shigella species possess a type III secretion system (T3SS), which is required for human infection and that delivers effector proteins into target host cells. Here, we show that the effector, IpaH4.5 dampens the pro-inflammatory cytokine response. In both the Sereny test and a murine lung infection model, the Shigella ?ipaH4.5 mutant strain caused more severe inflammatory responses and significantly induced higher pro-inflammatory cytokine levels (MIP-2 and TNF-?) in the lung homogenates of wild type-infected mice. Moreover, there was a threefold decrease in bacterial colonization of the mutant compared with the WT and ?ipaH4.5/ipaH4.5-rescued strains. Yeast two-hybrid screening showed that IpaH4.5 specifically interacts with the p65 subunit of NF-?B. Ten truncated versions of IpaH4.5 and p65 spanning different regions were constructed and expressed to further map the IpaH binding sites with p65. The results revealed thatthe p65 region spanning amino acids 1-190 of p65 interacted with the IpaH4.5/1-293 N-terminal region. In vitro, IpaH4.5 displayed ubiquitin ligase activity towards ubiquitin and p65. Furthermore, the transcriptional activity of NF-?B was shown to be inhibited by IpaH4.5 utilizing a dual-luciferase reporter gene detection system containing NF-?B promoter response elements. Thus, we conclude that the IpaH4.5 protein is an E3 ubiquitin ligase capable of directly regulating the host inflammatory response by inhibiting the NF-?B signalling pathway.
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LuxS-dependent AI-2 regulates versatile functions in Enterococcus faecalis V583.
J. Proteome Res.
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Bacteria utilize a quorum sensing (QS) system to coordinate gene expression by monitoring the concentration of molecules known as autoinducers (AI). In the present study, we confirmed the presence of a LuxS/AI-2 dependent QS system in vancomycin-resistant Enterococcus faecalis V583. Then, the cellular targets controlled by AI-2 were identified by comparative proteomics analysis in order to elucidate the possible role of AI-2 in E. faecalis. Results demonstrated 15 proteins that are differentially expressed upon the addition of AI-2, including proteins involved in metabolism, translation, energy production and/or conversion, and cell wall biogenesis. Glyceraldehyde-3-phosphate dehydrogenase and malate dehydrogenase associated with carbohydrate metabolism and energy production were up-regulated upon inducing by AI-2. In addition, externally added AI-2 could down-regulate acetyl-coenzyme A carboxylase and ornithine carbamoyltransferase, two key enzyme involved in metabolism. All these data suggest that AI-2 signaling may play a role in the regulation of a number of important metabolic properties of E. faecali. We further investigated the role of AI-2 in biofilm formation by E. faecalis, showing the addition of AI-2 to E. faecalis V583 cultures resulted in increased biofilm formation. Our results provide important clues to the role of a LuxS/AI-2 dependent QS system in vancomycin-resistant E. faecalis.
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Techniques for estimating health care costs with censored data: an overview for the health services researcher.
Clinicoecon Outcomes Res
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The aim of this study was to review statistical techniques for estimating the mean population cost using health care cost data that, because of the inability to achieve complete follow-up until death, are right censored. The target audience is health service researchers without an advanced statistical background.
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Proteomic analysis of clinical isolate of Stenotrophomonas maltophilia with blaNDM-1, blaL1 and blaL2 ?-lactamase genes under imipenem treatment.
J. Proteome Res.
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The co-occurrence of L1 and AmpR-L2 with bla(NDM-1) gene with an upstream 250-bp promoter was detected in a clinical isolate of Stenotrophomonas maltophilia DCPS-01, which was resistant to all ?-lactams and sensitive only to colistin and fluoroquinolones. To investigate expression of resistance genes and the molecular mechanisms of bacteria resistance to carbapenems, proteomic profiles of the isolate was passaged with and without the drug by using 2D-PAGE. The results showed that 33 genes exhibiting a ?3-fold change were identified as candidates that may help S. maltophilia survive drug selection. Strikingly, L1 was expressed more highly in cells grown with imipenem, and the abundant NDM-1 further increased, while very little L2 was detected even following induction. Specific activities for ?-lactamase revealed that L2 remained at constitutive low levels (10.6 U/mg), while L1 and NDM-1 showed clear activity (69.8 U/mg). Our data support that imipenem could specifically and reversibly induce L1 and NDM-1, which together played key roles in drug resistance in DCPS-01. Although NDM-1 mediated resistance to carbapenems has been found in very few cases, to our knowledge, this is the first proteomics research of S. maltophilia with NDM-1, giving very broad-spectrum antibiotic resistance profiles.
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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.