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101.
102.
Krzysztof Lacek Richard A. Urbanowicz Fulvia Troise Claudia De Lorenzo Valeria Severino Antimo Di Maro Alexander W. Tarr Francesca Ferrara Alexander Ploss Nigel Temperton Jonathan K. Ball Alfredo Nicosia Riccardo Cortese Antonello Pessi 《The Journal of biological chemistry》2014,289(50):35015-35028
The broadly neutralizing antibodies HIV 2F5 and 4E10, which bind to overlapping epitopes in the membrane-proximal external region of the fusion protein gp41, have been proposed to use a two-step mechanism for neutralization; first, they bind and preconcentrate at the viral membrane through their long, hydrophobic CDRH3 loops, and second, they form a high affinity complex with the protein epitope. Accordingly, mutagenesis of the CDRH3 can abolish their neutralizing activity, with no change in the affinity for the peptide epitope. We show here that we can mimic this mechanism by conjugating a cholesterol group outside of the paratope of an antibody. Cholesterol-conjugated antibodies bind to lipid raft domains on the membrane, and because of this enrichment, they show increased antiviral potency. In particular, we find that cholesterol conjugation (i) rescues the antiviral activity of CDRH3-mutated 2F5, (ii) increases the antiviral activity of WT 2F5, (iii) potentiates the non-membrane-binding HIV antibody D5 10–100-fold (depending on the virus strain), and (iv) increases synergy between 2F5 and D5. Conjugation can be made at several positions, including variable and constant domains. Cholesterol conjugation therefore appears to be a general strategy to boost the potency of antiviral antibodies, and, because membrane affinity is engineered outside of the antibody paratope, it can complement affinity maturation strategies. 相似文献
103.
104.
V. Severino A. Paiardini S. Pascarella A. Parente A. Chambery 《International journal of biological macromolecules》2009,45(4):407-413
Volkensin, isolated from Adenia volkensii, is one of the most toxic type 2 ribosome-inactivating protein (RIP), exerting its biological function by inhibiting protein synthesis. Despite the high sequence identity with type 2 RIPs, including ricin, volkensin shows interesting peculiar properties.In this work a computational model building of volkensin was performed. The volkensin electrostatic potential charge distribution, the hydrophobic profile and the surface topology analyses were also carried out to aid the understanding of structure–function relationships of this potent toxin. Volkensin surface topology was probed by applying a limited proteolysis approach with the aim to gain insights into volkensin conformational features. 相似文献
105.
Gopal Kedia José A. Vázquez Dimitris Charalampopoulos Severino S. Pandiella 《Current microbiology》2009,58(4):338-342
The prebiotic potential of oat samples was investigated by in vitro shaker-flask anaerobic fermentations with human fecal
cultures. The oat bran fraction was obtained by debranning and was compared with other carbon sources such as whole oat flour,
glucose, and fructo-oligosaccharide. The oat bran fraction showed a decrease in culturable anaerobes and clostridia and an
increase in bifidobacteria and lactobacilli populations. A similar pattern was observed in fructo-oligosaccharide. Butyrate
production was higher in oat bran compared to glucose and similar to that in fructo-oligosaccharide. Production of propionate
was higher in the two oat media than in fructo-oligosaccharide and glucose, which can be used as energy source by the liver.
This study suggests that the oat bran fraction obtained by debranning is digested by the gut ecosystem and increases the population
of beneficial bacteria in the indigenous gut microbiota. This medium also provides an energy source preferred by colonocytes
when it is metabolized by the gut flora. 相似文献
106.
Determinants of participation restriction among community dwelling stroke survivors: A path analysis
Background
Apart from promoting physical recovery and assisting in activities of daily living, a major challenge in stroke rehabilitation is to minimize psychosocial morbidity and to promote the reintegration of stroke survivors into their family and community. The identification of key factors influencing long-term outcome are essential in developing more effective rehabilitation measures for reducing stroke-related morbidity. The aim of this study was to test a theoretical model of predictors of participation restriction which included the direct and indirect effects between psychosocial outcomes, physical outcome, and socio-demographic variables at 12 months after stroke. 相似文献107.
108.
A sample of fixed bacterial cells was examined by immunofluorescence microscopy using an Alexa 488 conjugated secondary antibody for visualization. Excitation using visible light confirmed the expected photostability of this fluorophore; however, when using 2-photon excitation, Alexa 488 was rapidly and substantially photobleached. The unexpected instability of Alexa 488 under certain conditions may have deleterious consequences if not anticipated and accommodated in experimental protocols. 相似文献
109.
João Carlos Shimada Borges Paola Cristina Branco Leandro Nogueira Pressinotti Divinomar Severino José Roberto Machado Cunha da Silva 《Polar Biology》2010,33(6):843-849
Because of human actions, biomarkers have become important to detect and mitigate pollution. This study showed that crystalloids
can be a biomarker for analyses of low levels of water-soluble fractions of oil (WSF). Antarctic sea urchins (Sterechinus neumayeri) from regions free of pollution were exposed for 2, 5, 10 and 15 days at different levels of WSF (0.4, 0.8 and 1.2 ppm).
No significant differences were observed in the phagocytic rates or the germicide capacity for the yeast Saccharomyces cerevisiae; however, there was a significant increase in the quantity of intranuclear iron crystalloids in phagocytic amoebocytes of
urchins exposed to higher levels of WSF. This study characterizes histological alterations in crystalloids of S. neumayeri that could be used as a biomarker for oil contaminants, with a simple and inexpensive protocol. 相似文献
110.
Ferdinando Fiorino Beatrice Severino Francesca De Angelis Elisa Perissutti Elisa Magli Francesco Frecentese Antonella Esposito Paola Massarelli Cristina Nencini Vincenzo Santagada Giuseppe Caliendo 《Bioorganic & medicinal chemistry letters》2010,20(9):2978-2982
N′-Cyanoisonicotinamidine derivatives, linked to an arylpiperazine moiety, were prepared to identify highly selective and potent 5-HT1A ligands as potential pharmacological tools in studies of wide spread psychiatric disorders. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical in order to have affinity on 5-HT1A receptor and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT1A and moderate to no affinity for other relevant receptors (5-HT2A, 5-HT2C, D1, D2, α1 and α2). N′-Cyano-N-(3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)isonicotinamidine (4o) with Ki = 0.038 nM, was the most active and selective derivative for the 5-HT1A receptor with respect to other serotoninergic, dopaminergic and adrenergic receptors. 相似文献