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91.
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.92.
93.
94.
Differences in the chitinolytic activity of mammalian chitinases on soluble and insoluble substrates
Benjamin A. Barad Lin Liu Roberto E. Diaz Ralp Basilio Steven J. Van Dyken Richard M. Locksley James S. Fraser 《Protein science : a publication of the Protein Society》2020,29(4):952-963
Chitin is an abundant polysaccharide used by many organisms for structural rigidity and water repulsion. As such, the insoluble crystalline structure of chitin poses significant challenges for enzymatic degradation. Acidic mammalian chitinase, a processive glycosyl hydrolase, is the primary enzyme involved in the degradation of environmental chitin in mammalian lungs. Mutations to acidic mammalian chitinase have been associated with asthma, and genetic deletion in mice increases morbidity and mortality with age. We initially set out to reverse this phenotype by engineering hyperactive acidic mammalian chitinase variants. Using a screening approach with commercial fluorogenic substrates, we identified mutations with consistent increases in activity. To determine whether the activity increases observed were consistent with more biologically relevant chitin substrates, we developed new assays to quantify chitinase activity with insoluble chitin, and identified a one‐pot fluorogenic assay that is sufficiently sensitive to quantify changes to activity due to the addition or removal of a carbohydrate‐binding domain. We show that the activity increases from our directed evolution screen were lost when insoluble substrates were used. In contrast, naturally occurring gain‐of‐function mutations gave similar results with oligomeric and insoluble substrates. We also show that activity differences between acidic mammalian chitinase and chitotriosidase are reduced with insoluble substrate, suggesting that previously reported activity differences with oligomeric substrates may have been driven by differential substrate specificity. These results highlight the need for assays against physiological substrates when engineering metabolic enzymes, and provide a new one‐pot assay that may prove to be broadly applicable to engineering glycosyl hydrolases. 相似文献
95.
Susanne Siebentritt Enrico Avancini Marcus Br Jakob Bombsch Emilie Bourgeois Stephan Buecheler Romain Carron Celia Castro Sebastien Duguay Roberto Flix Evelyn Handick Dimitrios Hariskos Ville Havu Philip Jackson Hannu‐Pekka Komsa Thomas Kunze Maria Malitckaya Roberto Menozzi Milos Nesladek Nicoleta Nicoara Martti Puska Mohit Raghuwanshi Philippe Pareige Sascha Sadewasser Giovanna Sozzi Ayodhya Nath Tiwari Shigenori Ueda Arantxa Vilalta‐Clemente Thomas Paul Weiss Florian Werner Regan G. Wilks Wolfram Witte Max Hilaire Wolter 《Liver Transplantation》2020,10(8)
96.
Lorenzo Rossi Luca Sebastiani Roberto Tognetti Riccardo d’Andria Giovanni Morelli Paolo Cherubini 《Plant and Soil》2013,372(1-2):567-579
Background and Aims
Olive tree (Olea europaea L.) is a drought-tolerant tree species cultivated in Mediterranean-type environments. Although it is tolerant to drought, dry conditions decrease its productivity. A thorough analysis of the hydraulic architecture and wood anatomical plasticity, as well as of their physiological significance, is needed to understand how olive trees will adapt to the predicted increase in frequency and severity of drought in the Mediterranean region.Methods
Dendrochronological, stable isotopic (δ13C, δ18O) and wood anatomical analyses were applied to understand how different water availability can affect wood stem structure and function, in rainfed and irrigated at 100 % of crop evapotranspiration (ETc) olive trees in an experimental orchard close to Benevento (Italy) from 1992 to 2009.Results
Dendrochronological data indicate that cross-dating and synchronization of ring-width time series in olive tree is possible. After the start of irrigation, significantly more negative δ13C and lower δ18O values were recorded in irrigated trees indicating higher stomatal conductance and transpiration rates. Increased water balance induced the formation of a higher number of vessels with higher diameter.Conclusions
Water balance variations affected wood anatomy and isotopic composition. Anatomical analyses detected structural and functional adjustments in rainfed trees that produced more vessels with lower diameter to prevent cavitation. Isotopic analyses confirmed that irrigated trees continuously showed enhanced transpiration rates. 相似文献97.
Catalina López-Bastidas Elena Smolentseva Vitalii Petranovskii Roberto Machorro 《Plasmonics (Norwell, Mass.)》2013,8(4):1551-1558
The plasmonic features in the optical response of coinage metal nanoparticles supported on different type of zeolites were studied. The shifts in the plasmon frequency were analyzed for Cu, Ag, and Au nanoparticles in mordenite, β-zeolite, and Y-zeolite. It was shown experimentally that the resonance energy is sensitive both to type of zeolite structure and counter-cation of zeolite, as well as to annealing temperature and chemical composition of zeolite, their SiO2/Al2O3 molar ratio. A theoretical framework was employed to identify physical mechanism for this sensitivity. Within a simple model, the width of the absorption window identified in the imaginary part of the bulk dielectric function of the different metals was seen to play the important role in establishing the range of the plasmon energies available. In terms of an effective dielectric function, the composite medium was fully described by the complex dielectric function of the metal involved, the dissipation-free dielectric function of the zeolite matrix, and the filling fraction which relates the volume of metal inclusions as a fraction of the total sample volume. The sensitivity of the optical spectra is understood in terms of variations in both the dielectric response of the zeolite matrix as well as nanoparticle size. 相似文献
98.
Di Fiore R Guercio A Puleio R Di Marco P Drago-Ferrante R D'Anneo A De Blasio A Carlisi D Di Bella S Pentimalli F Forte IM Giordano A Tesoriere G Vento R 《Journal of cellular biochemistry》2012,113(11):3380-3392
Osteosarcoma is the second leading cause of cancer‐related death for children and young adults. In this study, we have subcutaneously injected—with and without matrigel—athymic mice (Fox1nu/nu) with human osteosarcoma 3AB‐OS pluripotent cancer stem cells (CSCs), which we previously isolated from human osteosarcoma MG63 cells. Engrafted 3AB‐OS cells were highly tumorigenic and matrigel greatly accelerated both tumor engraftment and growth rate. 3AB‐OS CSC xenografts lacked crucial regulators of beta‐catenin levels (E‐cadherin, APC, and GSK‐3beta), and crucial factors to restrain proliferation, resulting therefore in a strong proliferation potential. During the first weeks of engraftment 3AB‐OS‐derived tumors expressed high levels of pAKT, beta1‐integrin and pFAK, nuclear beta‐catenin, c‐Myc, cyclin D2, along with high levels of hyperphosphorylated‐inactive pRb and anti‐apoptotic proteins such as Bcl‐2 and XIAP, and matrigel increased the expression of proliferative markers. Thereafter 3AB‐OS tumor xenografts obtained with matrigel co‐injection showed decreased proliferative potential and AKT levels, and undetectable hyperphosphorylated pRb, whereas beta1‐integrin and pFAK levels still increased. Engrafted tumor cells also showed multilineage commitment with matrigel particularly favoring the mesenchymal lineage. Concomitantly, many blood vessels and muscle fibers appeared in the tumor mass. Our findings suggest that matrigel might regulate 3AB‐OS cell behavior providing adequate cues for transducing proliferation and differentiation signals triggered by pAKT, beta1‐integrin, and pFAK and addressed by pRb protein. Our results provide for the first time a mouse model that recapitulates in vivo crucial features of human osteosarcoma CSCs that could be used to test and predict the efficacy in vivo of novel therapeutic treatments. J. Cell. Biochem. 113: 3380–3392, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
99.
100.
Roberto Arredondo-Valdés Francisco D. Hernández-Castillo Mario Rocandio-Rodríguez Julia C. Anguiano-Cabello Madai Rosas-Mejía Venancio Vanoye-Eligio Salvador Ordaz-Silva Imelda V. López-Sánchez Laura D. Carrazco-Peña Julio C. Chacón-Hernández 《Phyton》2021,90(3):895-906
The tomato (Solanum lycopersicum L.) is one of the world’s most important vegetable crops. Still, phytopathogenic bacteria affect the yield and quality of tomato cultivation, like Agrobacterium tumefeciens (At), Clavibacter
michiganensis subsp. michiganensis (Cmm), Pseudomonas syringae pv. tomato (Pst), Ralstonia solanacearum (Rs),
and Xanthomonas axonopodis (Xa). Synthetic chemical products are used mostly on disease plant control, but
overuse generates resistance to bacterial control. This study aimed to evaluate the in vitro antibacterial activity
of the ethanolic extract of Moringa oleifera Lam. leaves against At, Cmm, Pst, Rs, and Xa, as well as information
about this plant species’ chemical composition. Antibacterial activity against pathogens observed by microplate
technique, phytochemical screening, and FTIR analysis revealed different bio-active compounds on ethanolic
extracts with antibacterial activity. The growth inhibition rate ranged between 0.08% and 99.94%. The inhibitory
concentration, IC50, required to inhibit 50% of At, Cmm, Pst, Rs, and Xa bacterial growth, was 276.67, 350.48,
277.85, 351.49, and 283.22 mg/L, respectively. Inhibition of phytopathogen bacteria’s growth increased as the concentrations of the extract also increased. Moringa oleifera extract can be recommended as a potent bio-bactericide. 相似文献