Isoarnottinin 4′-glucoside, a glycosylated coumarin from Prangos uloptera, with biological activity

Coumarins are a well-known group of natural products distributed in the plant kingdom especially in the family Apiaceae with various biological activities. Isoarnottinin 4′-glucoside is a simple glycosylated coumarin found previously in a few genera of Apiaceae, and its biological activities have not been previously described in details. In the present paper, the compound was isolated from Prangos uloptera (Apiaceae) leaves using HPLC techniques. Antimicrobial, phytotoxic and cytotoxic activities of the compound were evaluated by disk diffusion, lettuce assay and MTT method. Our results indicated that the compound has high antibacterial effect against Erwinia carotovora, a common plant pathogen with MIC value of 100 μg/ml. The compound also exhibited significant phytotoxic activity against lettuce and modest cytotoxic activity against HeLa cell line with IC₅₀ of 0.84 mg/ml. It could be concluded that isoarnottinin 4′-glucoside may play phytoalexin or allelopathic role for plant and may be a candidate for an antibacterial agent or a bioherbicide.     

Characterisation of capacitive field-effect sensors with a nanocrystalline-diamond film as transducer material for multi-parameter sensing

The feasibility of a capacitive field-effect EDIS (electrolyte-diamond-insulator-semiconductor) platform for multi-parameter sensing is demonstrated by realising EDIS sensors with an O-terminated nanocrystalline-diamond (NCD) film as transducer material for the detection of pH and penicillin concentration as well as for the label-free electrical monitoring of adsorption and binding of charged macromolecules, like polyelectrolytes. The NCD films were grown on p-Si-SiO(2) substrates by microwave plasma-enhanced chemical vapour deposition. To obtain O-terminated surfaces, the NCD films were treated in an oxidising medium. The NCD-based field-effect sensors have been characterised by means of constant-capacitance method. The average pH sensitivity of the O-terminated NCD film was 40 mV/pH. A low detection limit of 5 microM and a high penicillin G sensitivity of 65-70 mV/decade has been obtained for an EDIS penicillin biosensor with the adsorptively immobilised enzyme penicillinase. Alternating potential changes, having tendency to decrease with increasing the number of adsorbed polyelectrolyte layers, have been observed after the layer-by-layer deposition of polyelectrolyte multilayers, using positively charged PAH (poly (allylamine hydrochloride)) and a negatively charged PSS (poly (sodium 4-styrene sulfonate)) as a model system. The response mechanism of the developed EDIS sensors is discussed.     

Isoarnottinin 4'-glucoside, a glycosylated coumarin from Prangos uloptera, with biological activity

Coumarins are a well-known group of natural products distributed in the plant kingdom especially in the family Apiaceae with various biological activities. Isoarnottinin 4'-glucoside is a simple glycosylated coumarin found previously in a few genera of Apiaceae, and its biological activities have not been previously described in details. In the present paper, the compound was isolated from Prangos uloptera (Apiaceae) leaves using HPLC techniques. Antimicrobial, phytotoxic and cytotoxic activities of the compound were evaluated by disk diffusion, lettuce assay and MTT method. Our results indicated that the compound has high antibacterial effect against Erwinia carotovora, a common plant pathogen with MIC value of 100 microg/mL. The compound also exhibited significant phytotoxic activity against lettuce and modest cytotoxic activity against HeLa cell line with IC50 of 0 .84 mg/mL. It could be concluded that isoamottinin 4'-glucoside may play phytoalexin or allelopathic role for plant and may be a candidate for an antibacterial agent or a bioherbicide.     

Developing an emulsion model system containing canthaxanthin biosynthesized by Dietzia natronolimnaea HS-1

An acceptable strategy to incorporate canthaxanthin (CX) as a natural colorant into products is by means of oil-in-water emulsions. The used CX in this study was produced by bacterium Dietzia natronolimnaea HS-1 using a batch bioreactor system. A central composite rotatable design-response surface methodology (CCRD-RSM) consisting of three-factored factorial design with five levels was applied for analysis of the results to obtain the optimal formulation of emulsions. Three independent variables including fenugreek gum (FG, 0.2-0.5%, w/w), coconut oil (CO, 6-10%, w/w), and CO/CX ratio (10:1-50:1) were transformed to coded values and second-order polynomial models was developed to predict the responses (p<0.0001). The studied independent variables were the stability, viscosity and droplet size properties such as volume-weighted mean diameter (D(43)), specific surface area (S(v)) and polydispersity index (PDI) of emulsions. The 3-D response surface plot derived from the mathematical models was used to determine the optimal conditions. Main emulsion components under the optimum conditions ascertained presently by RSM: 50:1 CO/CX ratio, 0.49% (w/w) FG content and 6.28% (w/w) CO concentration. At this optimum point, stability, viscosity, D(43), S(v) and PDI were 90.6%, 0.0118Pas, 0.595μm, 12.03m(2)/ml and 1.380, respectively.     

Analyses of the Redistribution of Work following Cardiac Resynchronisation Therapy in a Patient Specific Model

Regulation of regional work is essential for efficient cardiac function. In patients with heart failure and electrical dysfunction such as left branch bundle block regional work is often depressed in the septum. Following cardiac resynchronisation therapy (CRT) this heterogeneous distribution of work can be rebalanced by altering the pattern of electrical activation. To investigate the changes in regional work in these patients and the mechanisms underpinning the improved function following CRT we have developed a personalised computational model. Simulations of electromechanical cardiac function in the model estimate the regional stress, strain and work pre- and post-CRT. These simulations predict that the increase in observed work performed by the septum following CRT is not due to an increase in the volume of myocardial tissue recruited during contraction but rather that the volume of recruited myocardium remains the same and the average peak work rate per unit volume increases. These increases in the peak average rate of work is is attributed to slower and more effective contraction in the septum, as opposed to a change in active tension. Model results predict that this improved septal work rate following CRT is a result of resistance to septal contraction provided by the LV free wall. This resistance results in septal shortening over a longer period which, in turn, allows the septum to contract while generating higher levels of active tension to produce a higher work rate.     

Study of natural diversity in response to a key pathogenicity regulator of Ralstonia solanacearum reveals new susceptibility genes in Arabidopsis thaliana

Ralstonia solanacearum gram-negative phytopathogenic bacterium exerts its virulence through a type III secretion system (T3SS) that translocates type III effectors (T3Es) directly into the host cells. T3E secretion is finely controlled at the posttranslational level by helper proteins, T3SS control proteins, and type III chaperones. The HpaP protein, one of the type III secretion substrate specificity switch (T3S4) proteins, was previously highlighted as a virulence factor on Arabidopsis thaliana Col-0 accession. In this study, we set up a genome-wide association analysis to explore the natural diversity of response to the hpaP mutant of two A. thaliana mapping populations: a worldwide collection and a local population. Quantitative genetic variation revealed different genetic architectures in both mapping populations, with a global delayed response to the hpaP mutant compared to the GMI1000 wild-type strain. We have identified several quantitative trait loci (QTLs) associated with the hpaP mutant inoculation. The genes underlying these QTLs are involved in different and specific biological processes, some of which were demonstrated important for R. solanacearum virulence. We focused our study on four candidate genes, RKL1, IRE3, RACK1B, and PEX3, identified using the worldwide collection, and validated three of them as susceptibility factors. Our findings demonstrate that the study of the natural diversity of plant response to a R. solanacearum mutant in a key regulator of virulence is an original and powerful strategy to identify genes directly or indirectly targeted by the pathogen.     

Cytotoxic and apoptotic properties of a novel nano-toxin formulation based on biologically synthesized silver nanoparticle loaded with recombinant truncated pseudomonas exotoxin A

Bacterial toxins have received a great deal of attention in the development of antitumor agents. Currently, these protein toxins were used in the immunotoxins as a cancer therapy strategy. Despite the successful use of immunotoxins, immunotherapy strategies are still expensive and limited to hematologic malignancies. In the current study, for the first time, a nano-toxin comprised of truncated pseudomonas exotoxin (PE38) loaded silver nanoparticles (AgNPs) were prepared and their cytotoxicity effect was investigated on human breast cancer cells. The PE38 protein was cloned into pET28a and expressed in Escherichia coli, BL21 (DE3), and purified using metal affinity chromatography and was analyzed by 15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AgNPs were biologically prepared using cell-free supernatant of E. Coli K12 strain. Nanoparticle formation was characterized by energy dispersive spectroscopy, transmission electron microscopy, and dynamic light scattering. The PE38 protein was loaded on AgNPs and prepared the PE38-AgNPs nano-toxin. Additionally, in vitro release indicated a partial slow release of toxin in about 100 hr. The nano-toxin exhibited dose-dependent cytotoxicity on MCF-7 cells. Also, real-time polymerase chain reaction results demonstrated the ability of nano-toxin to upregulate Bax/Bcl-2 ratio and caspase-3, -8, -9, and P53 apoptotic genes in the MCF-7 tumor cells. Apoptosis induction was determined by Annexin-V/propidium flow cytometry and caspases activity assay after treatment of cancer cells with the nano-toxin. In general, in the current study, the nano-toxin exhibit an inhibitory effect on the viability of breast cancer cells through apoptosis, which suggests that AgNPs could be used as a delivery system for targeting of toxins to cancer cells.     

Measurement of total pulmonary arterial compliance using invasive pressure monitoring and MR flow quantification during MR-guided cardiac catheterization

Pulmonary hypertensive disease is assessed by quantification of pulmonary vascular resistance. Pulmonary total arterial compliance is also an indicator of pulmonary hypertensive disease. However, because of difficulties in measuring compliance, it is rarely used. We describe a method of measuring pulmonary arterial compliance utilizing magnetic resonance (MR) flow data and invasive pressure measurements. Seventeen patients with suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment underwent MR-guided cardiac catheterization. Invasive manometry was used to measure pulmonary arterial pressure, and phase-contrast MR was used to measure flow at baseline and at 20 ppm nitric oxide (NO). Total arterial compliance was calculated using the pulse pressure method (parameter optimization of the 2-element windkessel model) and the ratio of stroke volume to pulse pressure. There was good agreement between the two estimates of compliance (r = 0.98, P < 0.001). However, there was a systematic bias between the ratio of stroke volume to pulse pressure and the pulse pressure method (bias = 61%, upper level of agreement = 84%, lower level of agreement = 38%). In response to 20 ppm NO, there was a statistically significant fall in resistance, systolic pressure, and pulse pressure. In seven patients, total arterial compliance increased >10% in response to 20 ppm NO. As a population, the increase did not reach statistical significance. There was an inverse relation between compliance and resistance (r = 0.89, P < 0.001) and between compliance and mean pulmonary arterial pressure (r = 0.72, P < 0.001). We have demonstrated the feasibility of quantifying total arterial compliance using an MR method.     

Mechanisms of Lipid Scrambling by the G Protein-Coupled Receptor Opsin

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Estimation of passive and active properties in the human heart using 3D tagged MRI

Advances in medical imaging and image processing are paving the way for personalised cardiac biomechanical modelling. Models provide the capacity to relate kinematics to dynamics and—through patient-specific modelling—derived material parameters to underlying cardiac muscle pathologies. However, for clinical utility to be achieved, model-based analyses mandate robust model selection and parameterisation. In this paper, we introduce a patient-specific biomechanical model for the left ventricle aiming to balance model fidelity with parameter identifiability. Using non-invasive data and common clinical surrogates, we illustrate unique identifiability of passive and active parameters over the full cardiac cycle. Identifiability and accuracy of the estimates in the presence of controlled noise are verified with a number of in silico datasets. Unique parametrisation is then obtained for three datasets acquired in vivo. The model predictions show good agreement with the data extracted from the images providing a pipeline for personalised biomechanical analysis.