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21.
Toward a general mixed quantum/classical method for the calculation of the vibronic ECD of a flexible dye molecule with different stable conformers: Revisiting the case of 2,2,2‐trifluoro‐anthrylethanol 下载免费PDF全文
Javier Cerezo Daniel Aranda Francisco J. Avila Ferrer Giacomo Prampolini Giuseppe Mazzeo Giovanna Longhi Sergio Abbate Fabrizio Santoro 《Chirality》2018,30(6):730-743
We extend a recently proposed mixed quantum/classical method for computing the vibronic electronic circular dichroism (ECD) spectrum of molecules with different conformers, to cases where more than one hindered rotation is present. The method generalizes the standard procedure, based on the simple Boltzmann average of the vibronic spectra of the stable conformers, and includes the contribution of structures that sample all the accessible conformational space. It is applied to the simulation of the ECD spectrum of (S)‐2,2,2‐trifluoroanthrylethanol, a molecule with easily interconvertible conformers, whose spectrum exhibits a pattern of alternating positive and negative vibronic peaks. Results are in very good agreement with experiment and show that spectra averaged over all the sampled conformational space can deviate significantly from the simple average of the contributions of the stable conformers. The present mixed quantum/classical method is able to capture the effect of the nonlinear dependence of the rotatory strength on the molecular structure and of the anharmonic couplings among the modes responsible for molecular flexibility. Despite its computational cost, the procedure is still affordable and promises to be useful in all cases where the ECD shape arises from a subtle balance between vibronic effects and conformational variety. 相似文献
22.
Anna Maria Dursi Stefania Albrizio Giovanni Greco Sonia Mazzeo Maria R Mazzoni Etrore Novellino Paolo Rovero 《Journal of peptide science》2002,8(8):476-488
The C-terminal domain of the heterotrimeric G protein a-subunits plays a key role in selective activation of G proteins by their cognate receptors. Several C-terminal fragments of Galpha(s) (from 11 to 21 residues) were recently synthesized. The ability of these peptides to stimulate agonist binding was found to be related to their size. Galpha(s)(380-394) is a 15-mer peptide of intermediate length among those synthesized and tested that displays a biological activity surprisingly weak compared with that of the corresponding 21-mer peptide, shown to be the most active. In the present investigation, Galpha(s)(380-394) was subjected to a conformational NMR analysis in a fluorinated isotropic environment. An NMR structure, calculated on the basis of the data derived from conventional 1D and 2D homonuclear experiments, shows that the C-terminal residues of Galpha(s)(380-394) are involved in a helical arrangement whose length is comparable to that of the most active 21 -mer peptide. A comparative structural refinement of the NMR structures of Galpha(s)(380-394) and Galpha(s)(374-394)C379A was performed using molecular dynamics calculations. The results give structural elements to interpret the role played by both the backbone conformation and the side chain arrangement in determining the activity of the G protein C-terminal fragments. The orientation of the side chains allows the peptides to assume contacts crucial for the G protein/receptor interaction. In the 15-mer peptide the lack as well as the disorder of some N-terminal residues could explain the low biological activity observed. 相似文献
23.
Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for the Discrimination of Food-Borne Microorganisms 下载免费PDF全文
Maria Fiorella Mazzeo Alida Sorrentino Marcello Gaita Giuseppina Cacace Michele Di Stasio Angelo Facchiano Giuseppe Comi Antonio Malorni Rosa Anna Siciliano 《Applied microbiology》2006,72(2):1180-1189
A methodology based on matrix-assisted laser desorption ionization-time of flight mass spectrometry of intact bacterial cells was used for rapid discrimination of 24 bacterial species, and detailed analyses to identify Escherichia coli O157:H7 were carried out. Highly specific mass spectrometric profiles of pathogenic and nonpathogenic bacteria that are well-known major food contaminants were obtained, uploaded in a specific database, and made available on the Web. In order to standardize the analytical protocol, several experimental, sample preparation, and mass spectrometry parameters that can affect the reproducibility and accuracy of data were evaluated. Our results confirm the conclusion that this strategy is a powerful tool for rapid and accurate identification of bacterial species and that mass spectrometric methodologies could play an essential role in polyphasic approaches to the identification of pathogenic bacteria. 相似文献
24.
Multivesicular bodies (MVBs) are endocytic compartments that enclose intraluminal vesicles (ILVs) formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, these ILV contain Fas ligand (FasL) and are secreted as ''lethal exosomes'' following activation-induced fusion of the MVB with the plasma membrane. Diacylglycerol (DAG) and diacylglycerol kinase α (DGKα) regulate MVB maturation and polarized traffic, as well as subsequent secretion of pro-apoptotic exosomes, but the molecular basis underlying these phenomena remains unclear. Here we identify protein kinase D (PKD) family members as DAG effectors involved in MVB genesis and secretion. We show that the inducible secretion of exosomes is enhanced when a constitutively active PKD1 mutant is expressed in T lymphocytes, whereas exosome secretion is impaired in PKD2-deficient mouse T lymphoblasts and in PKD1/3-null B cells. Analysis of PKD2-deficient T lymphoblasts showed the presence of large, immature MVB-like vesicles and demonstrated defects in cytotoxic activity and in activation-induced cell death. Using pharmacological and genetic tools, we show that DGKα regulates PKD1/2 subcellular localization and activation. Our studies demonstrate that PKD1/2 is a key regulator of MVB maturation and exosome secretion, and constitutes a mediator of the DGKα effect on MVB secretory traffic.Exosomes are nanovesicles that form as intraluminal vesicles (ILVs) inside multivesicular bodies (MVBs) and are then secreted by numerous cell types.1 ILVs are generated by inward budding of late endosome limiting membrane in a precisely regulated maturation process.2, 3 Two main pathways are involved in MVB maturation.4, 5 In addition to the ESCRT (endosomal complex required for traffic) proteins,6 there is increasing evidence that lipids such as lyso-bisphosphatidic acid (LBPA),7 ceramides8 and diacylglycerol (DAG)9 contribute to this membrane invagination process.Exosomes participate in many biological processes related to T-cell receptor (TCR)-triggered immune responses, including T lymphocyte-mediated cytotoxicity and activation-induced cell death (AICD), antigen presentation and intercellular miRNA exchange.10, 11, 12, 13, 14, 15 The discovery of exosome involvement in these responses increased interest in the regulation of exosome biogenesis and secretory traffic, with special attention to the contribution of lipids such as ceramide and DAG, as well as DAG-binding proteins.14, 16, 17, 18, 19, 20, 21 These studies suggest that positive and negative DAG regulators may control secretory traffic. By transforming DAG into phosphatidic acid (PA), diacylglycerol kinase α (DGKα) is essential for the negative control of DAG function in T lymphocytes.22 DGKα translocates transiently to the T-cell membrane after human muscarinic type 1 receptor (HM1R) triggering or to the immune synapse (IS) after TCR stimulation; at these subcellular locations, DGKα acts as a negative modulator of phospholipase C (PLC)-generated DAG.23, 24The secretory vesicle pathway involves several DAG-controlled checkpoints at which DGKα may act; these include vesicle formation and fission at the trans-Golgi network (TGN), MVB maturation, as well as their transport, docking and fusion to the plasma membrane.9, 16, 17, 18, 19, 20 The molecular components that regulate some of these trafficking processes include protein kinase D (PKD) family members.21 PKD1 activity, for instance, regulates fission of transport vesicles from TGN via direct interaction with the pre-existing DAG pool at this site.19 The cytosolic serine/threonine kinases PKD1, PKD2 and PKD3(ref. 21) are expressed in a wide range of cells, with PKD2 the most abundant isotype in T lymphocytes.25, 26 PKD have two DAG-binding domains (C1a and C1b) at the N terminus,21 which mediate PKD recruitment to cell membranes. Protein kinase C (PKC) phosphorylation at the PKD activation loop further promotes PKD autophosphorylation and activation.27Based on our previous studies showing DGKα regulation of DAG in MVB formation and exosome secretion,9, 14, 28 and the identification of PKD1/2 association to MVB,14 we hypothesized that DGKα control of DAG mediates these events, at least in part, through PKD. Here we explored whether, in addition to its role in vesicle fission from TGN,19 PKD regulates other steps in the DAG-controlled secretory traffic pathway. Using PKD-deficient cell models, we analyzed the role of PKD1/2 in MVB formation and function, and demonstrate their implication in exosome secretory traffic. 相似文献
25.
I. Mazzeo E. Giorgini G. Gioacchini F. Maradonna M. C. Vílchez S. Baloche S. Dufour L. Pérez O. Carnevali J. F. Asturiano 《Journal of fish biology》2016,89(4):2055-2069
A multi‐technique approach was used to study the changes occurring in European eel Anguilla anguilla ovaries during hormonally‐induced vitellogenesis. Aside from classic techniques used to monitor the vitellogenic process, such as ovary histology, fat content analysis, sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) and vitellogenin enzyme linked immunosorbent assay (ELISA), a new technique, Fourier‐transform infrared (FT‐IR) microspectroscopy, was used to analyse A. anguilla ovaries. The results from the different techniques provided different ways of approaching the same process. Although it is considered a time consuming approach, of all the employed techniques, histology provided the most direct evidences about vitellogenesis. SDS–PAGE and ELISA were also useful for studying vitellogenesis, whereas fat analysis cannot be used for this purpose. The FT‐IR analysis provided a representative IR spectrum for each ovarian stage (previtellogenic stage, early vitellogenic stage, mid‐vitellogenic stage and late vitellogenic stage), demonstrating that it is a valid method able to illustrate the distribution of the oocytes within the ovary slices. The chemical maps obtained confirmed changes in lipid concentrations and revealed their distribution within the oocytes at different maturational stages. When the results and the accuracy of the FT‐IR analysis were compared with those of the traditional techniques commonly used to establish the vitellogenic stage, it became evident that FT‐IR is a useful and reliable tool, with many advantages, including the fact that it requires little biological material, the costs involved are low, analysis times are short and last but not least, the fact that it offers the possibility of simultaneously analysing various biocomponents of the same oocyte. 相似文献
26.
Sarian Kosten Gissell Lacerot Erik Jeppesen David da Motta Marques Egbert H. van Nes Nestor Mazzeo Marten Scheffer 《Ecosystems》2009,12(7):1117-1129
A positive feedback between submerged vegetation and water clarity forms the backbone of the alternative state theory in shallow
lakes. The water clearing effect of aquatic vegetation may be caused by different physical, chemical, and biological mechanisms
and has been studied mainly in temperate lakes. Recent work suggests differences in biotic interactions between (sub)tropical
and cooler lakes might result in a less pronounced clearing effect in the (sub)tropics. To assess whether the effect of submerged
vegetation changes with climate, we sampled 83 lakes over a gradient ranging from the tundra to the tropics in South America.
Judged from a comparison of water clarity inside and outside vegetation beds, the vegetation appeared to have a similar positive
effect on the water clarity across all climatic regions studied. However, the local clearing effect of vegetation decreased
steeply with the contribution of humic substances to the underwater light attenuation. Looking at turbidity on a whole-lake
scale, results were more difficult to interpret. Although lakes with abundant vegetation (>30%) were generally clear, sparsely
vegetated lakes differed widely in clarity. Overall, the effect of vegetation on water clarity in our lakes appears to be
smaller than that found in various Northern hemisphere studies. This might be explained by differences in fish communities
and their relation to vegetation. For instance, unlike in Northern hemisphere studies, we find no clear relation between vegetation
coverage and fish abundance or their diet preference. High densities of omnivorous fish and coinciding low grazing pressures
on phytoplankton in the (sub)tropics may, furthermore, weaken the effect of vegetation on water clarity. 相似文献
27.
S.V. Soriano N.B. Pierangeli L. Pianciola M. Mazzeo L.E. Lazzarini M.S. Saiz A.V. Kossman H.F.J. Bergagna K. Chartier J.A. Basualdo 《Parasitology international》2010,59(4):626-628
Human cystic echinococcosis is a highly endemic zoonotic disease in the province of Neuquén, Patagonia Argentina, although a hydatid control programme has been carried out since 1970. Human infection due to Echinococcus canadensis (G6 genotype) is frequent in Neuquén. However, the reservoir for this species remains undetermined in a region where camels are absent. We investigated the fertility, viability and molecular epidemiology of hydatid cysts obtained from local goats, pigs and sheep in order to identify the possible reservoirs of E. canadensis (G6). We also analyzed isolates from infected dogs. A total of 67 isolates were identified by the DNA sequencing of the mitochondrial cytochrome c oxidase subunit 1 gene. Cysts from sheep (n = 16), goats (n = 23) and pigs (n = 18) and adult worms from 10 infected dogs were analyzed. The fertility of the hydatid cysts was 78.6%; 90.4% and 94.4% for sheep, goats and pigs, respectively. We detected E. canadensis (G6) in 21 of 23 goat samples and in 1 dog isolate, E. canadensis (G7) in all the pig isolates, E. granulosus sensu stricto (G3) in 1 sheep and the G1 genotype in 15 sheep, 2 goats and 9 dog samples. The G1 haplotypes included the common sheep strain sequence and 2 microvariants of this sequence. E. granulosus sensu stricto (G3) is described for the first time in South America. We conclude that goats act as reservoir for E. canadensis (G6) in Neuquén, and that control strategies may have to be adapted to local molecular epidemiology to improve the control of parasite transmission. 相似文献
28.
Hongwei Xie Asish Chakraborty Joomi Ahn Ying Qing Yu Deepalakshmi P Dakshinamoorthy Martin Gilar Weibin Chen St John Skilton Jeffery R Mazzeo 《MABS-AUSTIN》2010,2(4):379-394
This study shows that state-of-the-art liquid chromatography (LC) and mass spectrometry (MS) can be used for rapid verification of identity and characterization of sequence variants and posttranslational modifications (PTMs) for antibody products. A candidate biosimilar IgG1 monoclonal antibody (mAb) was compared in detail to a commercially available innovator product. Intact protein mass, primary sequence, PTMs and the micro-differences between the two mAbs were identified and quantified simultaneously. Although very similar in terms of sequences and modifications, a mass difference observed by LC-MS intact mass measurements indicated that they were not identical. Peptide mapping, performed with data independent acquisition LC-MS using an alternating low and elevated collision energy scan mode (LC-MSE), located the mass difference between the biosimilar and the innovator to a two amino acid residue variance in the heavy chain sequences. The peptide mapping technique was also used to comprehensively catalogue and compare the differences in PTMs of the biosimilar and innovator mAbs. Comprehensive glycosylation profiling confirmed that the proportion of individual glycans was different between the biosimilar and the innovator, although the number and identity of glycans were the same. These results demonstrate that the combination of accurate intact mass measurement, released glycan profiling and LC-MSE peptide mapping provides a set of routine tools that can be used to comprehensively compare a candidate biosimilar and an innovator mAb.Key words: biosimilar mAb, innovator mAb, molecular similarity, sequence variants, posttranslational modifications, N-linked glycosylation, chemical degradations, micro-heterogeneities, characterization, intact protein mass measurement, peptide mapping, glycan profiling, LC-MS, LC-fluorescence, MALDI MS 相似文献
29.
Ercole Mazzeo Laura Rubino Michela Buglione Paolo Antognoni Stefano Maria Magrini Francesco Bertoni Manuela Parmiggiani Paola Barbieri Filippo Bertoni 《Reports of Practical Oncology and Radiotherapy》2014,19(2):77-91
Aim
To evaluate the current treatment of mycosis fungoides (MF) and Sézary syndrome (SS) focusing on the role of radiotherapy (RT), its principles and indications, and the perspectives of the novel irradiation technologies.Background
MF and SS are rare lymphoproliferative diseases whose incidence is increasing. For a long time RT has been used as a single modality or in integrated treatment programs for these diseases.Materials and methods
The latest systematic reviews, primary studies and new diagnostic and treatment guidelines on MF and SS were analyzed. Clinical outcomes together with the technical aspects and the role of RT were also evaluated.Results
New data are available on pathogenesis, diagnostic criteria, classification and staging procedures for MF and SS and several local and systemic therapies are proposed. Localized RT can cure “minimal stage” MF while total skin electron beam irradiation (TSEI) may cure initial-stage disease and may offer important symptom relief (itch, erythroderma) in a more advanced setting. Despite its efficacy, RT is not largely used, mainly because of some technical difficulties but new RT technologies may be proposed to treat large skin surfaces.Conclusions
New treatment programs offer good results, with median survival of more than 12 years in early-stage MF, but the median survival of 2.5 years or less in advanced stages is still a challenge. RT remains an option for all stages with a good cost/effectiveness ratio in a curative or palliative setting. New RT technologies can overcome some technical problems of treating large skin surfaces. 相似文献30.
Angela Lombardi Michele Saviano Flavia Nastri Ornella Maglio Marco Mazzeo Carla Isernia Livio Paolillo Vincenzo Pavone 《Biopolymers》1996,38(6):693-703
In the present paper we describe the solution nmr structural analysis and restrained molecular dynamic simulation of the cyclic pentapeptide cyclo-(Pro-Phe-Phe-β-Ala-β-Ala). The conformational analysis carried out in CD3CN and dimethylsulfoxide (DMSO) solutions by nmr spectroscopy was based on interproton distances derived from rotating frame nuclear Overhauser effect spectroscopy spectra and homonuclear coupling constants. A restrained molecular dynamic simulation in vacuo was also performed to build refined molecular models. The molecule is present in both solvent systems as two slowly interconverting conformers, characterized by a cis-trans isomerism around the β-Ala5-Pro1 peptide bond. In CD3CN solution, the conformer with a cis peptide bond is quite similar to that observed in the solid state, while the conformer containing all trans peptide bonds is characterized by an intramolecular hydrogen bond stabilizing a C10- and a C13-ring structure. In DMSO solution, the trans isomer is partly similar to that observed in CD3CN solution while the cis isomer is different from that observed in the solid state. The effect of the solvent in stabilizing different conformations was also investigated in DMSO-CD3CN solvent mixtures. © 1996 John Wiley & Sons, Inc. 相似文献