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991.
Maaran Michael Rajah Mathieu Hubert Elodie Bishop Nell Saunders Remy Robinot Ludivine Grzelak Delphine Planas Jrmy Dufloo Stacy Gellenoncourt Alice Bongers Marija Zivaljic Cyril Planchais Florence GuivelBenhassine Franoise Porrot Hugo Mouquet Lisa A Chakrabarti Julian Buchrieser Olivier Schwartz 《The EMBO journal》2021,40(24)
Severe COVID‐19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS‐CoV‐2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighboring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha (B.1.1.7) and Beta (B.1.351) spread and fusion in cell cultures, compared with the ancestral D614G strain. Alpha and Beta replicated similarly to D614G strain in Vero, Caco‐2, Calu‐3, and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Variant spike proteins displayed higher ACE2 affinity compared with D614G. Alpha, Beta, and D614G fusion was similarly inhibited by interferon‐induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes modified fusogenicity, binding to ACE2 or recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS‐CoV‐2 emerging variants display enhanced syncytia formation. 相似文献
992.
993.
Interactions of atrazine and 2,4-D with human serum albumin studied by gel and capillary electrophoresis, and FTIR spectroscopy. 总被引:10,自引:0,他引:10
M Purcell J F Neault H Malonga H Arakawa R Carpentier H A Tajmir-Riahi 《Biochimica et biophysica acta》2001,1548(1):129-138
The herbicides 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine (atrazine) and 2,4-dichlorophenoxyacetic acid (2,4-D) are widely used in agricultural practice to fight dicotyledon weeds mainly in maize, cereals, and lucerne. As a result, these compounds are found not only in the plants, soil, and water, but also in the cultivated ground in the following years as well as in agricultural products such as fruits, milk, butter, and sugar beet. The toxicological effects of herbicides occur in vivo, when transported to the target organ through the bloodstream. It has been suggested that human serum albumin (HSA) serves as a carrier protein to transport 2,4-D to molecular targets. This study was designed to examine the interaction of atrazine and 2,4-D with HSA in aqueous solution at physiological pH with herbicide concentrations of 0.0001-1 mM, and final protein concentration of 1% w/v. Gel and capillary electrophoresis, UV-visible and Fourier transform infrared spectroscopic methods were used to determine the drug binding mode, the drug binding constant, and the protein secondary structure in aqueous solution. Structural analysis showed that different types of herbicide-HSA complexes are formed with stoichiometric ratios (drug/protein) of 3:1 and 11:1 for atrazine and 4.5:1 and 10:1 for 2,4-D complexes. Atrazine showed a weak binding affinity (K=3.50 x 10(4) M(-1)), whereas two bindings (K(1)=2.50 x 10(4) M(-1) and K(2)=8.0 x 10(3) M(-1)) were observed for 2,4-D complexes. The herbicide binding results in major protein secondary structural changes from that of the alpha-helix 55% to 45--39% and beta-sheet 22% to 24--32%, beta-anti 12% to 10--22% and turn 11% to 12--15%, in the drug-HSA complexes. The observed spectral changes indicate a partial unfolding of the protein structure, in the presence of herbicides in aqueous solution. 相似文献
994.
Philippine Chambault David Pinaud Vincent Vantrepotte Laurent Kelle Mathieu Entraygues Christophe Guinet Rachel Berzins Karin Bilo Philippe Gaspar Beno?t de Thoisy Yvon Le Maho Damien Chevallier 《PloS one》2015,10(9)
In response to seasonality and spatial segregation of resources, sea turtles undertake long journeys between their nesting sites and foraging grounds. While satellite tracking has made it possible to outline their migration routes, we still have little knowledge of how they select their foraging grounds and adapt their migration to dynamic environmental conditions. Here, we analyzed the trajectories and diving behavior of 19 adult green turtles (Chelonia mydas) during their post-nesting migration from French Guiana and Suriname to their foraging grounds off the coast of Brazil. First Passage Time analysis was used to identify foraging areas located off Ceará state of Brazil, where the associated habitat corresponds to favorable conditions for seagrass growth, i.e. clear and shallow waters. The dispersal and diving patterns of the turtles revealed several behavioral adaptations to the strong hydrodynamic processes induced by both the North Brazil current and the Amazon River plume. All green turtles migrated south-eastward after the nesting season, confirming that they coped with the strong counter North Brazil current by using a tight corridor close to the shore. The time spent within the Amazon plume also altered the location of their feeding habitats as the longer individuals stayed within the plume, the sooner they initiated foraging. The green turtles performed deeper and shorter dives while crossing the mouth of the Amazon, a strategy which would help turtles avoid the most turbulent upper surface layers of the plume. These adjustments reveal the remarkable plasticity of this green turtle population when reducing energy costs induced by migration. 相似文献
995.
M. C. Djoman J. F. Neault S. Hashemi-Fesharaky H. A. Tajmir-Riahi 《Journal of biomolecular structure & dynamics》2013,31(6):1115-1120
Abstract Ascorbic acid and divalent iron salts have been widely used to investigate the effects of reactive oxygen species in different biological targets such as nucleic acids, proteins and lipids. This study was designed to examine the interaction of yeast RNA with vitamin C in aqueous solution at physiological pH with drug/RNA(P)(P=phosphate) molar ratios of r= 1/80, 1/40, 1/20, 1/10, 1/4 and 1/2. Absorption spectra and Fourier transform infrared (FTIR) difference spectroscopy were used to determine the ascorbate binding mode, binding constant, sequence selectivity and RNA secondary structure in aqueous solution. Spectroscopic evidence showed that at low drug concentration (r=1/80 and 1/40), no major ascorbate-RNA interaction occurs, while at higher drug concentrations (r>1/40), a major drug-RNA complexation was observed through both G-C and A-U base pairs and the backbone phosphate groups with k=31.80 M?1. Evidence for this comes from large perturbations of the G-C vibrations at 1698 and 1488 cm?1 and the A-U bands at 1654 and 1608 cm?1 as well as the phosphate antisymmetric stretch at 1244 cm?1. At r>1/10, minor structural changes occur for the ribose-phosphate backbone geometry with RNA remaining in the A- family structure. The drug distributions around double helix were about 55% with G-C, 33% A-U and 12% with PO2 groups. A comparison between ascorbate-RNA and ascorbate-DNA complexes showed minor differences. The ascorbate binding (H-bonding) is via anion CO and OH groups. 相似文献
996.
Antoine Carof Virginie Marry Mathieu Salanne Jean-Pierre Hansen Pierre Turq 《Molecular simulation》2014,40(1-3):237-244
We investigate the possibility of describing by a continuous solvent model the dynamics of solutes confined down to the molecular scale. We derive a generalised Langevin equation (GLE) for the generic motion of a solute in an external potential using the Mori–Zwanzig formalism. We then compute the corresponding memory function from molecular simulations, in the case of cesium ions confined in the interlayer porosity of montmorillonite clays, with a very low water content (only six solvent molecules per ion). Previous attempts to describe the dynamics of cesium in this system by a simple Langevin equation were unsuccessful. The purpose of this work is not to carry out GLE simulations using the memory function from molecular simulations, but rather to analyse the separation of time scales between the confined ions and solvent. We show that such a separation is not achieved and discuss the relative contribution of the ion–surface, ion–solvent and ion–ion interactions to the dynamics. On the picosecond time scale, the ion oscillates in a surface-and-solvent cage, which relaxes on much longer time scales extending to several nanoseconds. The resulting overall dynamics resembles that of glasses or diffusion inside a solid by site-to-site hopping. 相似文献
997.
The µ opioid receptor (µOR), the principal target to control pain, belongs to the G protein-coupled receptors (GPCRs) family, one of the most highlighted protein families due to their importance as therapeutic targets. The conformational flexibility of GPCRs is one of their essential characteristics as they take part in ligand recognition and subsequent activation or inactivation mechanisms. It is assessed that the intrinsic mechanical properties of the µOR, more specifically its particular flexibility behavior, would facilitate the accomplishment of specific biological functions, at least in their first steps, even in the absence of a ligand or any chemical species usually present in its biological environment. The study of the mechanical properties of the µOR would thus bring some indications regarding the highly efficient ability of the µOR to transduce cellular message. We therefore investigate the intrinsic flexibility of the µOR in its apo-form using all-atom Molecular Dynamics simulations at the sub-microsecond time scale. We particularly consider the µOR embedded in a simplified membrane model without specific ions, particular lipids, such as cholesterol moieties, or any other chemical species that could affect the flexibility of the µOR. Our analyses highlighted an important local effect due to the various bendability of the helices resulting in a diversity of shape and volume sizes adopted by the µOR binding site. Such property explains why the µOR can interact with ligands presenting highly diverse structural geometry. By investigating the topology of the µOR binding site, a conformational global effect is depicted: the correlation between the motional modes of the extra- and intracellular parts of µOR on one hand, along with a clear rigidity of the central µOR domain on the other hand. Our results show how the modularity of the µOR flexibility is related to its pre-ability to activate and to present a basal activity. 相似文献
998.
Pauline Hamon Mathieu Paul Rodero Christophe Combadière Alexandre Boissonnas 《Journal of visualized experiments : JoVE》2015,(96)
Real time multiphoton imaging provides a great opportunity to study cell trafficking and cell-to-cell interactions in their physiological 3-dimensionnal environment. Biological activities of immune cells mainly rely on their motility capacities. Blood monocytes have short half-life in the bloodstream; they originate in the bone marrow and are constitutively released from it. In inflammatory condition, this process is enhanced, leading to blood monocytosis and subsequent infiltration of the peripheral inflammatory tissues. Identifying the biomechanical events controlling monocyte trafficking from the bone marrow towards the vascular network is an important step to understand monocyte physiopathological relevance. We performed in vivo time-lapse imaging by two-photon microscopy of the skull bone marrow of the Csf1r-Gal4VP16/UAS-ECFP (MacBlue) mouse. The MacBlue mouse expresses the fluorescent reporters enhanced cyan fluorescent protein (ECFP) under the control of a myeloid specific promoter 1, in combination with vascular network labelling. We describe how this approach enables the tracking of individual medullar monocytes in real time to further quantify the migratory behaviour within the bone marrow parenchyma and the vasculature, as well as cell-to-cell interactions. This approach provides novel insights into the biology of the bone marrow monocyte subsets and allows to further address how these cells can be influenced in specific pathological conditions. 相似文献
999.
Estimating the genetic variance available for traits informs us about a population’s ability to evolve in response to novel selective challenges. In selfing species, theory predicts a loss of genetic diversity that could lead to an evolutionary dead-end, but empirical support remains scarce. Genetic variability in a trait is estimated by correlating the phenotypic resemblance with the proportion of the genome that two relatives share identical by descent (‘realized relatedness’). The latter is traditionally predicted from pedigrees (ΦA: expected value) but can also be estimated using molecular markers (average number of alleles shared). Nevertheless, evolutionary biologists, unlike animal breeders, remain cautious about using marker-based relatedness coefficients to study complex phenotypic traits in populations. In this paper, we review published results comparing five different pedigree-free methods and use simulations to test individual-based models (hereafter called animal models) using marker-based relatedness coefficients, with a special focus on the influence of mating systems. Our literature review confirms that Ritland’s regression method is unreliable, but suggests that animal models with marker-based estimates of relatedness and genomic selection are promising and that more testing is required. Our simulations show that using molecular markers instead of pedigrees in animal models seriously worsens the estimation of heritability in outcrossing populations, unless a very large number of loci is available. In selfing populations the results are less biased. More generally, populations with high identity disequilibrium (consanguineous or bottlenecked populations) could be propitious for using marker-based animal models, but are also more likely to deviate from the standard assumptions of quantitative genetics models (non-additive variance). 相似文献
1000.
Mathieu Taillade Hélène Sauzéon Prashant Arvind Pala Marie Déjos Florian Larrue Christian Gross Bernard N’Kaoua 《PloS one》2013,8(7)
The aim of this study was to evaluate motor control activity (active vs. passive condition) with regards to wayfinding and spatial learning difficulties in large-scale spaces for older adults. We compared virtual reality (VR)-based wayfinding and spatial memory (survey and route knowledge) performances between 30 younger and 30 older adults. A significant effect of age was obtained on the wayfinding performances but not on the spatial memory performances. Specifically, the active condition deteriorated the survey measure in all of the participants and increased the age-related differences in the wayfinding performances. Importantly, the age-related differences in the wayfinding performances, after an active condition, were further mediated by the executive measures. All of the results relative to a detrimental effect of motor activity are discussed in terms of a dual task effect as well as executive decline associated with aging. 相似文献