Liposome destabilization induced by the HIV-1 fusion peptide Effect of a single amino acid substitution

AbstractThe 23-residue synthetic peptide representing the N-terminus of HIV-1 gp41 is known to induce either leakage or fusion of lipid vesicles depending on the experimental conditions. In this paper we report that a polar amino acid substitution V → E at position 2, known to block gp41 activity in vivo, makes the peptide unable to destabilize and/or fuse membranes. Moreover this variant, unlike the parent peptide, is never found in the membrane-associated β conformation

Experimental Research and Finite Element Modeling of 3-D Semi-Rigid Composite Joints under Proportional Loads

The behaviour of 2-D composite semi-rigid joints has been researched since the seventies, including experimental work, numerical models, analytical models and practical methods of analysis. However, one of the areas where research is still needed is in the three-dimensional behaviour of semi-rigid composite joints, that is, columns with beams attached to both axes (major and minor axis). This paper describes the details and the results of an experimental program consisting in a test of a 3D composite semi-rigid joint. The design of major axis connection is made with a bolted flush end plate connection while that of the minor axis is done by means of an additional plate welded to the column flanges, rather than attach it to the column web. The specimen is subjected to proportional loads, and further research will be done with non-proportional loads. A finite element (FE) model is developed and validated using the experimental results. The FE model will be used to perform a parametric study for three-dimensional semi-rigid composite joints subjected to proportional and non-proportional loads in a future research

Sugar inhibits the production of the toxins that trigger clostridial gas gangrene

Histotoxic strains of Clostridium perfringens cause human gas gangrene, a devastating infection during which potent tissue-degrading toxins are produced and secreted. Although this pathogen only grows in anaerobic-nutrient-rich habitats such as deep wounds, very little is known regarding how nutritional signals influence gas gangrene-related toxin production. We hypothesize that sugars, which have been used throughout history to prevent wound infection, may represent a nutritional signal against gas gangrene development. Here we demonstrate, for the first time, that sugars (sucrose, glucose) inhibited the production of the main protein toxins, PLC (alpha-toxin) and PFO (theta-toxin), responsible for the onset and progression of gas gangrene. Transcription analysis experiments using plc-gusA and pfoA-gusA reporter fusions as well as RT-PCR analysis of mRNA transcripts confirmed that sugar represses plc and pfoA expression. In contrast an isogenic C. perfringens strain that is defective in CcpA, the master transcription factor involved in carbon catabolite response, was completely resistant to the sugar-mediated inhibition of PLC and PFO toxin production. Furthermore, the production of PLC and PFO toxins in the ccpA mutant strain was several-fold higher than the toxin production found in the wild type strain. Therefore, CcpA is the primary or unique regulatory protein responsible for the carbon catabolite (sugar) repression of toxin production of this pathogen. The present results are analyzed in the context of the role of CcpA for the development and aggressiveness of clostridial gas gangrene and the well-known, although poorly understood, anti-infective and wound healing effects of sugars and related substances.Fil: Méndez, M. B.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; ArgentinaFil: Goñi, Anibal Juan. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Ramirez, W.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; ArgentinaFil: Grau, Roberto Ricardo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentin

Performance of baited underwater video for estimating abundance of spiny lobsters

Baited underwater video (BUV) is increasingly been used to sample fish species but lobsters are potentially good candidates for sampling with BUV as they are attracted to bait due to their scavenging habits. We built a cost effective BUV system to sample Palinurus elephas, a Mediterranean deep-water lobster. Camera deployments were performed at the Columbretes Islands MPA. We compared the standard method of estimating abundance with BUV, by recording the maximum number (Nmax) of individuals at any one point on the tape, with the estimated true number of lobsters having attended the bait (Ntot). We found it possible to use images of unique body patterns for identifying individuals over time. The highest Nmax - 6 lobsters in the field of view - was lower than the total number of lobsters estimated by identifying individuals in all three recordings - total of 7 to 11 individual lobsters. This highlights the extent of underestimation of abundance derived from Nmax estimates (Mean Nmax = 4 as opposed to Ntot= 8.6 by tracking individuals). Measurement of lobster size was trouble free with the coefficient of variation of all measurements being low. However, all measurements were biassed due to calibration problems related to lobster height above the bait bag. Taking into account the relatively low cost of the units, coupled with the ability of this system to work to depths impractical for visual surveys, we propose that this non-intrusive method will be useful for sampling deep water lobster

Monitoring the upper southeastern Atlantic transports using altimeter data

A large in-situ data set, collected in the southeastern Atlantic Ocean, is merged with the TOPEX/POSEIDON altimeter observations in order to verify the use of altimeter data in monitoring the transports of the Agulhas/Benguela system. Comparisons between altimeter observations and either moored current meters or inverted echo sounder measurements shows that the sea-surface elevation anomaly is significantly correlated with the thermocline depth and the surface dynamic height, respectively. Knowing the least-squares regression parameters, it is possible to calculate the transports by using geostrophy and either a two-layer or a continuously-stratified model. The transports obtained from fits of dynamic height to altimeter sea-surface height are similar to the ones calculated with the moored instruments. In the southern part of the area under analysis, around 35S, close to the Agulhas retroflection, the transports obtained from the two-layer model are overestimated. Across the Benguela Current, at 30S, transports are still overestimated but of the same order as the measured ones. In this part of the region, the two-layer model can be successfully used to calculate the total and barotropic transports of the Benguela Current. Analysis of the three years of geostrophic transport obtained from the altimeter data indicate that the mean Benguela Current transport does not change interannually more than 20%. However, the primary interannual variability derives from the source water that forms the Benguela Current

Contrasting sea-surface responses between the western Mediterranean Sea and eastern subtropical latitudes of the North Atlantic during abrupt climatic events of MIS 3

EuroCLIMATE project RESOLuTIONInternational audienceAbstract Dinoflagellate cyst (dinocyst) analysis was conducted on two cores from the SW Iberian margin and central Alboran Sea from which high quality records of Marine Isotope Stage 3 have been previously derived. Our aim in this study is to compare the dinocyst signature between 50 and 25 ka BP with existing datasets of foraminiferal and geochemical proxies related to hydrological parameters. Quantitative reconstructions of sea-surface temperatures (SSTs) and salinities (SSS) based on dinocysts are performed for the first time in this area. The results are compared to SSTs derived from planktonic foraminifera and alkenone measurements, and to SSS calculated from planktonic δ18O and foraminiferal SST. Significant oscillations related to Dansgaard-Oeschger cycles are recorded in both cores. Dinocyst-derived hydrological parameters exhibit synchronous fluctuations and similar values to those derived from the other methods, in particular when considering quantitative reconstructions for February based on foraminifera and dinocysts. Our study shows that the influence of subpolar waters was felt during each Greenland Stadial (GS) off Portugal, and that the amplification of the Heinrich Stadial cooling in the Alboran Sea was related to the penetration of subpolar waters through the Strait of Gibraltar. During Greenland Interstadials (GI), we provide evidence for the occurrence of warm and nutrient-rich sea-surface waters in the Alboran Sea, probably due to gyre-induced upwelling. Finally, the difference between August and February dinocyst SST estimates suggests higher seasonal contrasts during GS compared to GI at the two core sites. Additionally, precession appears to have an imprint on dinocyst-derived long-term seasonality record. However, this observation needs to be confirmed by longer records. Research Highlights ► We provide new dinocyst data on core MD95-2043 (Alboran Sea) during MIS 3. ► Quantitative dinocyst sea-surface parameters (SST, SSS) are reconstructed. ► A multi-proxies compilation (microfossils, alkenones, isotopes) is established. ► This dataset has been compared with the one of a SW Iberian margin core. ► Millennial-scale climatic variability is perfectly apparent from each side of Gibraltar

Coastal meroplanktonic larval stages of peninsula de Llevant natural reserve determined with light traps

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Bioavailability of two oral fentanyl transmucosal formulations in healthy volunteers: an open-label, crossover, randomised study.

Introduction: Oral transmucosal fentanyl citrate (OTFC) was the first product specifically designed for the treatment of breakthrough pain. It is formulated as a sweetened lozenge on a plastic handle (stick) and it is self-administered by the patient, allowing the modulability or flexibility in dosing. Objectives: To prove bioequivalence of a test (T) OTFC product compared to the reference (R) formulation. Material and methods: Open-label, crossover, randomized, single-dose bioequivalence study in healthy volunteers, with two study periods and two sequences, with a washout period of at least 10 days. On each study day, subjects received 400 μg of fentanyl. They were instructed to rub the tablet gently against the buccal mucosa and not to suck on or chew it, and the investigators controlled each administration to ensure that it was consumed during 15 minutes. Given the high pharmacokinetic variability, a two-stage design was established and bioequivalence decision was based on 94.12% confidence intervals of Cmax and AUC0-t geometric means ratio. Results: 36 subjects completed the study according to the protocol. Mean Cmax were similar with both formulations (814.78 pg/ml for T and 781.83 pg/ml for R) and were attained at the same time (40 min. for T and 50 min. for R), and their bioavailability was also very close (AUC0-t: 3920.12 pg.h/ml for T and 3679.39 pg.h/ml for R). Bioequivalence was confirmed for the two primary parameters, Cmax and AUC0-t. No period or sequence effects were observed in any parameter. As bioequivalence was proved in the first phase of the study, it was not necessary to proceed to the second stage. The estimated intraindividual variability was 24.66% and 19.01%, respectively for T and R formulations. Both formulations were well tolerated; 15 mild adverse events were reported. Discussion: The test OTFC product is bioequivalent to the reference one and therefore interchangeable when used clinically. OTFC administration provides faster fentanyl absorption than enteral route and the rate of absorption can be modulated by the administration technique, providing a unique flexibility among all breakthrough pain treatments. The results showed a fast time to maximum concentrations (tmax), in accordance with those originally reported for the reference product, probably favoured by the strict administration technique. Proper patient education is essential to optimize the use of OTFC, as well-trained patients can take advantage of its flexibility to selfcontrolling pain relief