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991.
Tommaso Banelli Marco Vuano Federico Fogolari Andrea Fusiello Gennaro Esposito Alessandra Corazza 《Journal of biomolecular NMR》2017,67(2):121-134
We describe a new algorithmic approach able to automatically pick and track the NMR resonances of a large number of 2D NMR spectra acquired during a stepwise variation of a physical parameter. The method has been named Trace in Track (TinT), referring to the idea that a gaussian decomposition traces peaks within the tracks recognised through 3D mathematical morphology. It is capable of determining the evolution of the chemical shifts, intensity and linewidths of each tracked peak.The performances obtained in term of track reconstruction and correct assignment on realistic synthetic spectra were high above 90% when a noise level similar to that of experimental data were considered. TinT was applied successfully to several protein systems during a temperature ramp in isotope exchange experiments. A comparison with a state-of-the-art algorithm showed promising results for great numbers of spectra and low signal to noise ratios, when the graduality of the perturbation is appropriate. TinT can be applied to different kinds of high throughput chemical shift mapping experiments, with quasi-continuous variations, in which a quantitative automated recognition is crucial. 相似文献
992.
Riccardo Rondanin Sara Fochi Riccardo Baruchello Tatiana Bernardi Paola Oliva Floriana Semeraro Daniele Simoni Giuseppe Giannini 《Bioorganic & medicinal chemistry letters》2017,27(18):4421-4425
The search for antimetastatic agents for cancer therapy may involve the ability of new compounds to maintain the tissue extracellular matrix integrity. Among known factors, heparanase, an endoglucuronidase responsible for heparan sulfate cleavage, is a promising target whose inhibition could represent a strong obstacle for metastatic cancerous mechanisms. The antimetastatic activity of some suramin derivatives reported in literature suggests a possible involvement of the heparanase enzyme. To confirm such hypothesis, we have investigated FCE27266, a molecule known for its antiangiogenic and antimetastatic properties. Other new derivatives were also synthesized and investigated. Our findings revealed that FCE27266 as well as some derivatives have a strong heparanase inhibition activity, together with no cytotoxic power. Moreover, a FCE27266 analogue (SST0546NA1; 17a) resulted also positive to lower gene expression of some proangiogenic factors. 相似文献
993.
Alessio Menga Maria Favia Iolanda Spera Maria C Vegliante Rosanna Gissi Anna De Grassi Luna Laera Annalisa Campanella Andrea Gerbino Giovanna Carr Marcella Canton Vera Loizzi Ciro L Pierri Gennaro Cormio Massimiliano Mazzone Alessandra Castegna 《EMBO reports》2021,22(9)
Glutaminolysis is known to correlate with ovarian cancer aggressiveness and invasion. However, how this affects the tumor microenvironment is elusive. Here, we show that ovarian cancer cells become addicted to extracellular glutamine when silenced for glutamine synthetase (GS), similar to naturally occurring GS‐low, glutaminolysis‐high ovarian cancer cells. Glutamine addiction elicits a crosstalk mechanism whereby cancer cells release N‐acetylaspartate (NAA) which, through the inhibition of the NMDA receptor, and synergistically with IL‐10, enforces GS expression in macrophages. In turn, GS‐high macrophages acquire M2‐like, tumorigenic features. Supporting this in␣vitro model, in silico data and the analysis of ascitic fluid isolated from ovarian cancer patients prove that an M2‐like macrophage phenotype, IL‐10 release, and NAA levels positively correlate with disease stage. Our study uncovers the unprecedented role of glutamine metabolism in modulating macrophage polarization in highly invasive ovarian cancer and highlights the anti‐inflammatory, protumoral function of NAA. 相似文献
994.
C Marino-Buslje G Venhudová M A Molina B Oliva X Jorba F Canals F X Avilés E Querol 《European journal of biochemistry》2000,267(5):1502-1509
The role of each residue of the potato carboxypeptidase inhibitor (PCI) C-terminal tail, in the interaction with carboxypeptidase A (CPA), has been studied by the analysis of two main kinds of site-directed mutants: the point substitution of each C-terminal residue by glycine and the sequential deletions of the C-terminal residues. The mutant PCI-CPA interactions have been characterized by the measurement of their inhibition constant, Ki, in several cases, by their kinetic association and dissociation constants determined by presteady-state analysis, and by computational approaches. The role of Pro36 appears to be mainly the restriction of the mobility of the PCI C-tail. In addition, and unexpectedly, both Gly35 and Pro36 have been found to be important for folding of the protein core. Val38 has the greatest enthalpic contribution to the PCI-CPA interaction. Although Tyr37 has a minor contribution to the binding energy of the whole inhibitor, it has been found to be essential for the interaction with the enzyme following the cleavage of the C-terminal Gly39 by CPA. The energetic contribution of the PCI secondary binding site has been evaluated to be about half of the total free energy of dissociation of the PCI-CPA complex. 相似文献
995.
John A. Carver Gennaro Esposito Paolo Viglino Federico Fogolari Gilles Guichard Jean-Paul Briand Marc H. V. Van Regenmortel Fred Brown Paolo Mascagni 《Biopolymers》1997,41(5):569-590
Antibodies induced against intact foot-and-mouth disease Virus (FMDV) particles bind to the retro-inverso analogue of fragment 141–159 of the viral coat protein VP1 of FMDV, variant A, equally well as to the parent peptide. A conformational investigation of this retro-inverso peptide was carried out by nmr spectroscopy and restrained molecular modeling in order to identify the structural basis for the antigenic mimicry between these retro-inverso and parent peptides. In 100% trifluoroethanol a well-defined left-handed α-helical region exists from residue 150 to residue 159, which is consistently present in all conformational families obtained from restrained modelling. A less-defined left-handed helical region is present in the tract 144–148, which is also consistent for all structures. Conformational flexibility exists about Gly149, which leads to two types of structures, either bent or linear. In the bent structures, a three-residue inverse tight turn is found, which can be classified as an inverse γ-turn centered at Gly149. The overall structural features of the retro-inverso peptide are shown to be similar to those of the parent L-peptide. The two molecules, however, are roughly mirror images because they share inherently chiral secondary structure elements. By comparing these conformational conclusions with the x-ray structure of the Fab complex of a corresponding VP1 antigenic fragment, a rationale is proposed to account for the topological requirements of specific recognition that are implied by the equivalent antigenic activity of the natural and retro-inverso compounds. © 1997 John Wiley & Sons, Inc. Biopoly 41: 569–590, 1997. 相似文献
996.
Alexandru Nicolae Ungureanu Luca Beratto Federico Abate Daga Gennaro Boccia Corrado Lupo Paolo Riccado Brustio 《Biology of sport / Institute of Sport》2022,39(3):621
In rugby union, physical characteristics may partially contribute to long-term career progression, especially during adolescence. Therefore, the primary purpose of the study was to evaluate Italian regional rugby union academy players’ (i.e., under-18) anthropometric and physical characteristics during a competitive season. Body mass, height, upper- and lower-body maximal strength, sprint, and high-intensity running ability were assessed in 29 elite players (backs, n = 13, forwards, n = 16). A mixed-design analysis of variance (ANOVA) for repeated measures showed that backs were shorter (ES = 0.59), lighter (ES = 0.94), stronger relative to body mass (bench press; ES = 0.60; deadlift; ES = 0.63; clean ES = 0.63; rowing ES = 0.67), and fitter (shuttle run max; ES = 0.38; shuttle run tot; ES = 0.79) than forwards. However, the forwards achieved greater sprint momentum (initial sprint momentum; ES = 0.97; maximal sprint momentum; ES = 0.98). During the season, players changed in stature, upper-body maximal strength, jumping, and high intensity running (p < 0.05), but not in body weight or lower-body maximal strength (p > 0.05). Maximal strength improved in the first part of the season, whereas jumping and sprinting performances increased in the last part of the season. Therefore, these findings highlight the importance of regularly monitoring the physical development in a long-term perspective, even suggesting that physiological adaptations are heterochronic between positional roles. 相似文献
997.
Federico Fogolari Serge Cattarinussi Gennaro Esposito Paolo Viglino 《Journal of biomolecular structure & dynamics》2013,31(3):629-635
Abstract The values of the different terms contributing to the free energy of a polyelectrolyte in ionic solution, calculated according to Manning's model are compared with those predicted by the Poisson—Boltzmann (P—B) equation solved for the cell model. On this ground, the limits of applicability of Manning's model and some of its features are discussed. The comparison confirms the usefulness of Manning's model for low charge density polyelectrolytes, while for higher charge densities some care should be used due to the breakdown of the approximations underlying the model. 相似文献
998.
A simple electrostatic model has been used to investigate the extent to which the structure of protein molecules is organized to optimize the internal electrostatic interactions. We find that the model provides a favorable total intra-protein electrostatic energy for almost all polar and charged groups of atoms, suggesting a high degree of structural optimization. By contrast, a significant fraction of individual group-group interactions are found to be unfavorable. An analysis as a function of the range of interactions included shows the electrostatic organization is generally relatively short range (up to 6 or 7 A between group centers). Although the model is very simple, it is useful for assessing the overall quality of protein experimental structures, for pin-pointing some types of errors and as a guide to improving protein design. 相似文献
999.
1000.