APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays ...also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.
Potentiometric pH miniaturized sensors based on electrosynthesized polypyrrole films were developped. These pH sensors consist in two interdigitated microarray electrodes which were fabricated using ...photolithography process. One electrode of the sensor is coated by a polypyrrole film while the other one is coated by a silver film used as reference electrode. The potentiometric responses of these sensors were generally linear to pH changes in the range from 2 to 11. More, some sensors appeared to be stable in time during 30 days. The effect of the thickness of polymer film to potentiometric responses was also studied. It appeared that thinner polypyrrole films gave better potentiometric responses than thicker ones.
•Synthesis of nanovectorized TRAIL by non-covalent grafting on oxidized SWCNT.•Characterization by STEM, Micro-Raman and XPS spectroscopies.•80% of TRAIL coverage on most oxidized SWCNT.•DFT ...calculations with van der Waals correction of ELF and DOS properties.•Good description of the physical adsorption on the sidewall of the SWCNT.
The synthesis and the characterization of a novel nanovector based on oxidized single-walled carbon nanotubes (SWCNT) functionalized with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via noncovalent 1-pyrenebutanoic acid N-hydrosuccinimid ester (PSE) is described. Experimental noncovalent functionalized SWCNT by PSE are compared to full DFT theoretical predictions. For this, several experimental techniques are gathered to prove the well functionalization of oxidized SWCNT by π–π stacking such as micro Raman and XPS spectroscopy analysis coupled to full-DFT calculations. Scanning transmission electron microscopy (STEM) coupled to energy dispersive spectroscopy (EDS) underline the presence of TRAIL ligands on the nanovector.
For most olfactometers described in the literature, adjusting olfactory stimulation intensity involves modifying the dilution of the odorant in a neutral solution (water, mineral, oil, etc.), the ...dilution of the odorant air in neutral airflow, or the surface of the odorant in contact with airflow. But, for most of these above-mentioned devices, manual intervention is necessary for adjusting concentration. We present in this article a method of controlling odorant concentration via a computer which can be implemented on even the most dynamic olfactometers. We used Pulse Width Modulation (PWM), a technique commonly used in electronic or electrical engineering, and we have applied it to odor delivery. PWM, when applied to odor delivery, comprises an alternative presentation of odorant air and clean air at a high frequency. The cycle period (odor presentation and rest) is 200 ms. In order to modify odorant concentration, the ratio between the odorant period and clean air presentation during a cycle is modified. This ratio is named duty cycle. Gas chromatography measurements show that this method offers a range of mixing factors from 33% to 100% (continuous presentation of odor). Proof of principle is provided via a psychophysical experiment. Three odors (isoamyl acetate, butanol and pyridine) were presented to twenty subjects. Each odor was delivered three times with five values of duty cycles. After each stimulation, the subjects were asked to estimate the intensity of the stimulus on a 10 point scale, ranging from 0 (undetectable) to 9 (very strong). Results show a main effect of the duty cycles on the intensity ratings for all tested odors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although the cerebral networks involved in sensory perception are of general interest in neuroscience, registration of the effects of olfactory stimulation, especially in a magnetic resonance imaging ...(MRI) environment, presents particular problems and constraints. This article presents details of a reliable and portable system for olfactory stimulation that is modular in design and based on microcontroller technology. It has the following characteristics: (1) It is under software control; (2) the presentation of olfactory stimulation can be synchronized with respiration; (3) it can be manually controlled; and (4) it is fully compatible with an MRI environment. The principle underlying this system is to direct an odor to the subject’s nostrils by switching airflow to different odor diffusers. The characteristics of this system were established using (1) ultraviolet (UV) spectroscopy, to measure its response time, and (2) gas chromatography, to measure the repeatability of odor presentation in terms of gas concentration. A response time of 200 ± 25 ms was obtained for the system, and the standard deviations of the gas concentration delivered during stimulation ranged from 1.5% to 22%, depending on the odor, the airflow, and the dilution of the odor used. Since it is portable, controlled by software, and reliable, on the basis of the results we obtained, this system will lend itself to a wide range of applications in olfactory neuroscience.
The retention mechanism of a series of peptides on a single‐wall carbon nanotube (SWCNT) stationary phase inside an HPLC column was investigated over a wide range of mobile phase compositions. While ...the similar size C18 column exhibited an efficiency of 11.5 μm, the SWCNT column increased the efficiency, i.e. 7.10 μm at a flow rate of 0.8 mL/min, and significantly affected the separation quality of the peptides. The values of enthalpy (ΔH) and entropy (ΔS*) of transfer of the peptides from the mobile to the SWCNT stationary phase were determined. The method studied each factor, i.e. ACN fraction x in the ACN/water mixture and column temperature. The changes in retention factor, ΔH and ΔS* as a function of the ACN fraction in the mobile phase were examined. These variations are explained using the organization of ACN in clusters in the ACN/water mixture and on the steric and electronic forces implied in the retention process. The information obtained in this work makes this SWCNT stationary phase useful for peptide research and demonstrated the role of ACN to improve the separation quality.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF cytokine superfamily. TRAIL is able to induce apoptosis through engagement of its death receptors DR4 and ...DR5 in a wide variety of tumor cells while sparing vital normal cells. This makes it a promising agent for cancer therapy. Here, we present two different ways of covalently grafting TRAIL onto maghemite nanoparticles (NPs): (a) by using carboxylic acid groups of the protein to graft it onto maghemite NPs previously functionalized with amino groups, and (b) by using the amino functions of the protein to graft it onto NPs functionalized with carboxylic acid groups. The two resulting nanovectors, NH-TRAIL@NPs-CO and CO-TRAIL@NPs-NH, were thoroughly characterized. Biological studies performed on human breast and lung carcinoma cells (MDA-MB-231 and H1703 cell lines) established these nanovectors are potential agents for cancer therapy. The pro-apoptotic effect is somewhat greater for CO-TRAIL@NPs-NH than NH-TRAIL@NPs-CO, as evidenced by viability studies and apoptosis analysis. A computational study indicated that regardless of whether TRAIL is attached to NPs through an acid or an amino group, DR4 recognition is not affected in either case.
A new sensing platform based on gold electrodes modified with reduced graphene oxide/polyethylenimine functionalized with anti-fimbrial E. coli antibodies is proposed for sensitive and selective ...electrochemical detection of uropathogenic E. coli in serum samples.
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•Electrophoretic deposition of reduced graphene oxide/polyethylenimine thin films on Au.•Functionalization with anti-fimbrial E. coli antibodies.•Uropathogenic E. coli electrochemical detection with high sensitivity and selectivity.•Bacteria detection in serum samples.
Fast, reliable and selective detection of microorganisms is of uttermost importance in clinical analysis, but also in food and water quality monitoring. In this study, we report on the construction of an immunosensor for sensitive and selective electrochemical detection of uropathogenic Escherichia coli (E. coli) UTI89 bacteria in aqueous and serum samples. We took benefit of electrophoretic deposition (EPD) to prepare, in a simple, controllable and cost effective way, gold electrodes modified with thin active layers of reduced graphene oxide/polyethylenimine (rGO/PEI). While rGO exhibits high surface area and favourable electrochemical properties, the presence of abundant NH2 groups on PEI offers a plethora of opportunities for the sensor’s surface functionalization. To achieve selectivity of detection, the electrode surface was covalently modified with anti-fimbrial E. coli antibodies via amide bond formation. To minimize non-specific adsorption, the immunosensor was additionally modified with pyrene-polyethyleneglycol (pyrene-PEG) moieties prior to antibody immobilization. The detection of E. coli was based on the restriction of electron transfer of a redox mediator, in our case potassium ferrocyanide, to the rGO/PEI modified electrical transducer due to the formation of an immune complex. The developed immunosensor displayed a sigmoidal shape with a linear range of 1 × 101–1 × 104 cfu mL−1 (R2 = 0.995) according to i(μA) = −16.66–20.5 × logE. coli (cfu mL−1) and a detection limit of 10 cfu mL−1. Additionally, the sensor performed well both in aqueous, serum and urine media, which is essential for its potential use for clinical diagnosis of pathogenic diseases. Selectivity studies showed that the immunosensor was able to discriminate between E. coli UTI89 wild-type strain and UTI89 Δfim, without fim operon.
Molecular dynamics simulations have been investigated to study the interactions between single-wall carbon nanotubes and an anticancer agent Pt complex (Cisplatin). The optimized diameter of the ...vector system has been determined to encapsulate in the best conditions the drug molecules. The simulation results show also that several drug molecules can be adsorbed inside the nanotubes, leading to an increased confinement time. Moreover, our simulations show that the release of the drug near a cell membrane model is favored, opening the way to a natural drug nanocapsule.
Antifungal polyenes such as nystatin (or amphotericin B) molecules play an important role in regulating ions permeability through membrane cell. The creation of self-assembled nanopores into the ...fungal lipid membranes permits the leakage and the selectivity of ions (i.e., blockage of divalent cations) that cause the cell death. These abilities are thus of first interest to promote new biomimetic membranes with improved ionic properties. In the present work, we will use molecular dynamic simulations to interpret recent experimental data that showed the transfer of the nystatin action inside artificial nanopore in terms of ion permeability and selectivity. We will demonstrate that nystatin polyenes can be stabilized in a hydrophobic carbon nanotube, even at high concentration. The high potential interaction between the polyenes and the hydrophobic pore wall ensures the apparition of a hole inside the biomimetic nanopore that changes its intrinsic properties. The probability ratios of cation versus anion show interesting reproducibility of experimental measurements and, to a certain extent, opened the way for transferring biological properties in synthetic membranes.
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