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51.
Atilla Akdemir Daniela Vullo Viviana De Luca Andrea Scozzafava Vincenzo Carginale Mosè Rossi Claudiu T. Supuran Clemente Capasso 《Bioorganic & medicinal chemistry letters》2013,23(4):1087-1090
The α-carbonic anhydrase (CA, EC 4.2.1.1) from the extremophilic bacterium Sulfurihydrogenibium azorense (SazCA) was recently shown to be the fastest CA known. Here we investigated this enzyme for its activation with a series of amino acids and amines. The best SazCA activators were d-Phe, l-DOPA, l- and d-Trp, dopamine and serotonin, which showed activation constants in the range of 3–23 nM. l- and d-His, l-Phe, l-Tyr, 2-pyridyl-methylamine and L-adrenaline were also effective activators (KAs in the range of 62–90 nM), whereas d-Dopa, d-Tyr and several heterocyclic amines showed activity in the micromolar range. The good thermal stability, robustness, very high catalytic activity and propensity to be activated by simple amino acids and amines, make SazCA a very interesting candidate for biomimetic CO2 capture processes. 相似文献
52.
Francesca Megiorni Giovanni Luca Gravina Simona Camero Simona Ceccarelli Andrea Del Fattore Vincenzo Desiderio Federica Papaccio Heather P. McDowell Rajeev Shukla Antonio Pizzuti Filip Beirinckx Philippe Pujuguet Laurent Saniere Ellen Van der Aar Roberto Maggio Francesca De Felice Cinzia Marchese Carlo Dominici Vincenzo Tombolini Claudio Festuccia Francesco Marampon 《Journal of hematology & oncology》2017,10(1):161
Background
EPH (erythropoietin-producing hepatocellular) receptors are clinically relevant targets in several malignancies. This report describes the effects of GLPG1790, a new potent pan-EPH inhibitor, in human embryonal rhabdomyosarcoma (ERMS) cell lines.Methods
EPH-A2 and Ephrin-A1 mRNA expression was quantified by real-time PCR in 14 ERMS tumour samples and in normal skeletal muscle (NSM). GLPG1790 effects were tested in RD and TE671 cell lines, two in vitro models of ERMS, by performing flow cytometry analysis, Western blotting and immunofluorescence experiments. RNA interfering experiments were performed to assess the role of specific EPH receptors. Radiations were delivered using an x-6 MV photon linear accelerator. GLPG1790 (30 mg/kg) in vivo activity alone or in combination with irradiation (2 Gy) was determined in murine xenografts.Results
Our study showed, for the first time, a significant upregulation of EPH-A2 receptor and Ephrin-A1 ligand in ERMS primary biopsies in comparison to NSM. GLPG1790 in vitro induced G1-growth arrest as demonstrated by Rb, Cyclin A and Cyclin B1 decrease, as well as by p21 and p27 increment. GLPG1790 reduced migratory capacity and clonogenic potential of ERMS cells, prevented rhabdosphere formation and downregulated CD133, CXCR4 and Nanog stem cell markers. Drug treatment committed ERMS cells towards skeletal muscle differentiation by inducing a myogenic-like phenotype and increasing MYOD1, Myogenin and MyHC levels. Furthermore, GLPG1790 significantly radiosensitized ERMS cells by impairing the DNA double-strand break repair pathway. Silencing of both EPH-A2 and EPH-B2, two receptors preferentially targeted by GLPG1790, closely matched the effects of the EPH pharmacological inhibition. GLPG1790 and radiation combined treatments reduced tumour mass by 83% in mouse TE671 xenografts.Conclusions
Taken together, our data suggest that altered EPH signalling plays a key role in ERMS development and that its pharmacological inhibition might represent a potential therapeutic strategy to impair stemness and to rescue myogenic program in ERMS cells.53.
Silvia Jane Lombardi Gianfranco Pannella Massimo Iorizzo Maria Victoria Moreno-Arribas Patrizio Tremonte Mariantonietta Succi Elena Sorrentino Vincenzo Macciola Massimo Di Renzo Raffaele Coppola 《World journal of microbiology & biotechnology》2018,34(11):161
In this study, the effect of sequential inoculation with non-Saccharomyces (Hanseniaspora guilliermondii) and Saccharomyces cerevisiae yeast on the distinctive characteristics of the Campanino white wine was investigated. For this purpose, three independent winemaking experiments were carried out on an industrial scale (batches A, B and C). In detail, the first one was carried out using the sequential inoculation technique while the other two, using a S. cerevisiae single-strain starter or no inoculation representing the control batches. Microbiological and chemical parameters and sensorial profiles of the wines were defined. Interestingly, the results showed that when sequential cultures (H. guilliermondii in a sequential mixture with S. cerevisiae) were used, a better wine aroma and quality was observed. More specifically, the wine obtained by sequential inoculation showed lower acetic acid values and enhanced volatile profiles than the wine from the control batches. Finally, sensorial analysis confirmed that the sequential cultures led to an improvement in wine flavour. Therefore, results suggest that the sequential inoculation using non-Saccharomyces and Saccharomyces yeast represents a biotechnological practice that can improve the quality features of traditional white wine. It has been shown for the first time that on an industrial scale H. guilliermondii could be used in sequential inoculum with S. cerevisiae in making white Campanino wine. 相似文献
Graphical abstract
54.
Cervellati C Franzoni L Squerzanti M Bergamini CM Spinozzi F Mariani P Lanzara V Spisni A 《Amino acids》2009,36(4):633-641
Activation of tissue transglutaminase by calcium involves a conformational change which allows exposition of the active site
to the substrate via movements of domains 3 and 4 that lead to an increase of the inter-domain distance. The inhibitor GTP
counteracts these changes. Here we investigate the possible existence of non-native conformational states still compatible
with the enzyme activity produced by chemical and thermal perturbations. The results indicate that chemical denaturation is
reversible at low guanidine concentrations but irreversible at high concentrations of guanidine. Indeed, at low guanidine
concentrations tissue TG-ase exists in a non-native state which is still affected by the ligands as in the native form. In
contrast, thermal unfolding is always irreversible, with aggregation and protein self-crosslinkage in the presence of calcium.
DSC thermograms of the native protein in the absence of ligands consist of two partly overlapped transitions, which weaken
in the presence of calcium and merge together and strengthen in the presence of GTP. Overall, the present work shows, for
the first time, the reversible denaturation of a TG-ase isoenzyme and suggests the possibility that also in in vivo, the enzyme
may acquire non-native conformations relevant to its patho-physiological functions. 相似文献
55.
Drumo R Widmer G Morrison LJ Tait A Grelloni V D'Avino N Pozio E Cacciò SM 《Applied and environmental microbiology》2012,78(10):3523-3529
Recent studies have revealed extensive genetic variation among isolates of Cryptosporidium parvum, an Apicomplexan parasite that causes gastroenteritis in both humans and animals worldwide. The parasite's population structure is influenced by the intensity of transmission, the host-parasite interaction, and husbandry practices. As a result, C. parvum populations can be panmictic, clonal, or even epidemic on both a local scale and a larger geographical scale. To extend the study of C. parvum populations to an unexplored region, 173 isolates of C. parvum collected in Italy from humans and livestock (calf, sheep, and goat) over a 10-year period were genotyped using a multilocus scheme based on 7 mini- and microsatellite loci. In agreement with other studies, extensive polymorphism was observed, with 102 distinct multilocus genotypes (MLGs) identified among 173 isolates. The presence of linkage disequilibrium, the confinement of MLGs to individual farms, and the relationship of many MLGs inferred using network analysis (eBURST) suggest a predominantly clonal population structure, but there is also evidence that part of the diversity can be explained by genetic exchange. MLGs from goats were found to differ from bovine and sheep MLGs, supporting the existence of C. parvum subpopulations. Finally, MLGs from isolates collected between 1997 and 1999 were also identified as a distinct subgroup in principal-component analysis and eBURST analysis, suggesting a continuous introduction of novel genotypes in the parasite population. 相似文献
56.
Rawson PM Molette C Videtta M Altieri L Franceschini D Donato T Finocchi L Propato A Paroli M Meloni F Mastroianni CM d'Ettorre G Sidney J Sette A Barnaba V 《Nature medicine》2007,13(12):1431-1439
We found that the proteome of apoptotic T cells includes prominent fragments of cellular proteins generated by caspases and that a high proportion of distinct T cell epitopes in these fragments is recognized by CD8+ T cells during HIV infection. The frequencies of effector CD8+ T cells that are specific for apoptosis-dependent epitopes correlate with the frequency of circulating apoptotic CD4+ T cells in HIV-1-infected individuals. We propose that these self-reactive effector CD8+ T cells may contribute to the systemic immune activation during chronic HIV infection. The caspase-dependent cleavage of proteins associated with apoptotic cells has a key role in the induction of self-reactive CD8+ T cell responses, as the caspase-cleaved fragments are efficiently targeted to the processing machinery and are cross-presented by dendritic cells. These findings demonstrate a previously undescribed role for caspases in immunopathology. 相似文献
57.
Kaido T Yebra M Cirulli V Montgomery AM 《The Journal of biological chemistry》2004,279(51):53762-53769
Collagens have been shown to influence the survival and function of cultured beta-cells; however, the utilization and function of individual collagen receptors in beta-cells is largely unknown. The integrin superfamily contains up to five collagen receptors, but we have determined that alpha(1)beta(1) is the primary receptor utilized by both fetal and adult beta-cells. Cultured beta-cells adhered to and migrated on collagen type IV (Col-IV), and these responses were mediated almost exclusively by alpha(1)beta(1). The migration of cultured beta-cells to Col-IV significantly exceeded that to other matrix components suggesting that this substrate is of unique importance for beta-cell motility. The interaction of alpha(1)beta(1) with Col-IV also resulted in significant insulin secretion at basal glucose concentrations. A subset of beta-cells in developing islets was confirmed to express alpha(1)beta(1), and this expression co-localized with Col-IV in the basal membranes of juxtaposed endothelial cells. Our findings indicate that alpha(1)beta(1) and Col-IV contribute to beta-cell functions known to be important for islet morphogenesis and glucose homeostasis. 相似文献
58.
Pasquale V Romano VJ Rupnik M Dumontet S Cižnár I Aliberti F Mauri F Saggiomo V Krovacek K 《Folia microbiologica》2011,56(5):431-437
This pilot study was carried out to evaluate the occurrence of Clostridium difficile in marine environments and in edible shellfish. Samples of seawater, sediment, and zooplankton were collected at five sampling
stations in the Gulf of Naples. Six samples of edible shellfish, furthermore, were obtained: two from mussel farms and four
from wholesalers. The isolation and the characterization of C. difficile strains were carried out using selective media and molecular techniques, respectively. C. difficile was isolated from nine of the 21 samples investigated. Shellfish and zooplankton showed the highest prevalence of positive
samples. No C. difficile was detected in marine sediment. Majority of the C. difficile isolates were toxin A/B positive. Six known different PCR ribotypes (003, 005, 009, 010, 056, and 066) were identified, whereas
one strain may represent a new PCR ribotype. C. difficile may be present in the marine environment in Southern Italy, including shellfish and zooplankton. This study is reporting
the isolation of C. difficile from zooplankton, clams, and mussels and pointing out a new possible route to exposure to C. difficile of healthy individuals in the community. 相似文献
59.
This article presents an immune inspired algorithm to tackle the Multiple Sequence Alignment (MSA) problem. MSA is one of the most important tasks in biological sequence analysis. Although this paper focuses on protein alignments, most of the discussion and methodology may also be applied to DNA alignments. The problem of finding the multiple alignment was investigated in the study by Bonizzoni and Vedova and Wang and Jiang, and proved to be a NP-hard (non-deterministic polynomial-time hard) problem. The presented algorithm, called Immunological Multiple Sequence Alignment Algorithm (IMSA), incorporates two new strategies to create the initial population and specific ad hoc mutation operators. It is based on the 'weighted sum of pairs' as objective function, to evaluate a given candidate alignment. IMSA was tested using both classical benchmarks of BAliBASE (versions 1.0, 2.0 and 3.0), and experimental results indicate that it is comparable with state-of-the-art multiple alignment algorithms, in terms of quality of alignments, weighted Sums-of-Pairs (SP) and Column Score (CS) values. The main novelty of IMSA is its ability to generate more than a single suboptimal alignment, for every MSA instance; this behaviour is due to the stochastic nature of the algorithm and of the populations evolved during the convergence process. This feature will help the decision maker to assess and select a biologically relevant multiple sequence alignment. Finally, the designed algorithm can be used as a local search procedure to properly explore promising alignments of the search space. 相似文献
60.
Viggiano E Passavanti MB Pace MC Sansone P Spaziano G Viggiano A Aurilio C Monda M Viggiano A Pota V De Luca B De Luca E 《Journal of cellular physiology》2012,227(5):1988-1991
Glutamine (gln) is the most abundant free amino acid in the blood. It is involved in important metabolic and biochemical processes, like cell proliferation and oxidative stress. Previous studies have demonstrated that gln concentration in human plasma decreases in several conditions such as sepsis, ischemia-reperfusion, trauma, major surgery and burn. The aim of the present work was to compare the acute effects of different types of surgical interventions and of anesthetization on blood gln concentration. Plasma samples from 88 subjects (30 males and 58 females) were collected before and after major or minor surgery and the gln concentration was analyzed with high-performance liquid chromatography. The results showed that plasma gln concentration after surgery was lower than pre-surgery values and that in major surgery the decrease of gln was higher than in minor surgery. No significant effect was shown for sex or type of anesthesia. These results demonstrate the importance of a gln supplementation before a surgical intervention and show that the amount of gln supplementation should also be adjusted based on the type of surgery. 相似文献