Look at a list of IC publications: 2019, 2018, 2017, 2016, 2015, 2014
2019 |
|
Lucilla Pronti Martina Romani, Gianluca Verona-Rinati Ombretta Tarquini Francesco Colao Marcello Colapietro Augusto Pifferi Mariangela Cestelli-Guidi Marco Marinelli Hermitage, 2 (3), pp. 2275-2286, 2019. @article{Pronti2019, title = {Post-Processing of VIS, NIR, and SWIR Multispectral Images of Paintings. New Discovery on the The Drunkenness of Noah, Painted by Andrea Sacchi, Stored at Palazzo Chigi (Ariccia, Rome) }, author = { Lucilla Pronti, Martina Romani, Gianluca Verona-Rinati, Ombretta Tarquini, Francesco Colao, Marcello Colapietro, Augusto Pifferi, Mariangela Cestelli-Guidi, Marco Marinelli}, doi = {10.3390/heritage2030139}, year = {2019}, date = {2019-08-02}, journal = {Hermitage}, volume = {2}, number = {3}, pages = {2275-2286}, abstract = {IR Reflectography applied to the identification of hidden details of paintings is extremely useful for authentication purposes and for revealing technical hidden features. Recently, multispectral imaging has replaced traditional imaging techniques thanks to the possibility to select specific spectral ranges bringing out interesting details of the paintings. VIS\textendashNIR\textendashSWIR images of one of the The Drunkenness of Noah versions painted by Andrea Sacchi, acquired with a modified reflex and InGaAs cameras, are presented in this research. Starting from multispectral images we performed post-processing analysis, using visible and infrared false-color images and principal component analysis (PCA) in order to highlight pentimenti and underdrawings. Radiography was performed in some areas to better investigate the inner pictorial layers. This study represents the first published scientific investigation of The Drunkenness of Noah’s artistic production, painted by Andrea Sacchi.}, keywords = {}, pubstate = {published}, tppubtype = {article} } IR Reflectography applied to the identification of hidden details of paintings is extremely useful for authentication purposes and for revealing technical hidden features. Recently, multispectral imaging has replaced traditional imaging techniques thanks to the possibility to select specific spectral ranges bringing out interesting details of the paintings. VIS–NIR–SWIR images of one of the The Drunkenness of Noah versions painted by Andrea Sacchi, acquired with a modified reflex and InGaAs cameras, are presented in this research. Starting from multispectral images we performed post-processing analysis, using visible and infrared false-color images and principal component analysis (PCA) in order to highlight pentimenti and underdrawings. Radiography was performed in some areas to better investigate the inner pictorial layers. This study represents the first published scientific investigation of The Drunkenness of Noah’s artistic production, painted by Andrea Sacchi. | |
Belviso, Benny Danilo ; Caliandro, Rosanna ; Salehi, Shabnam Majidi ; Di Profio, Gianluca ; Caliandro, Rocco Protein Crystallization in Ionic-Liquid Hydrogel Composite Membranes Journal Article Crystals, 9 (5), pp. 253, 2019, ISBN: 073-4352. @article{cryst9050253b, title = {Protein Crystallization in Ionic-Liquid Hydrogel Composite Membranes }, author = {Belviso, Benny Danilo and Caliandro, Rosanna and Salehi, Shabnam Majidi and Di Profio, Gianluca and Caliandro, Rocco}, doi = {10.3390/cryst9050253}, isbn = {073-4352}, year = {2019}, date = {2019-05-17}, journal = {Crystals}, volume = {9}, number = {5}, pages = {253}, abstract = {Protein crystallization is a powerful purification tool. It is the first step for crystallographic structural investigations, and can be preparatory for biotechnological applications. However, crystallizing proteins is challenging and methods to control the crystallization process are needed. Ionic-liquid hydrogel composite membranes (IL-HCMs) have been used here as material capable of supporting protein crystallization and hosting grown crystals. We found that IL-HCMs affect the selection mechanism of glucose isomerase (GI) polymorphs and make GI crystals grow completely immersed into the hydrogel layer. X-ray diffraction studies show that IL ions do not bind to the protein, likely because IL molecules are constrained in the polymeric framework. Our GI crystal structures have been compared with many existing GI crystal structures using multivariate analysis tools, allowing a comprehensive overview of factors determining structural similarities, i.e., temperature variations and external stresses exerted during or after crystal growth, such as dehydration or presence of hydrogel of a different nature. GI crystals grown on IL-HCM fit perfectly in this framework, showing typical features induced by external forces. Overall, protein crystallization by IL-HCMs show potential for biotechnological applications, as it could constitute a natural means for containing crystallized enzymes in working conditions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Protein crystallization is a powerful purification tool. It is the first step for crystallographic structural investigations, and can be preparatory for biotechnological applications. However, crystallizing proteins is challenging and methods to control the crystallization process are needed. Ionic-liquid hydrogel composite membranes (IL-HCMs) have been used here as material capable of supporting protein crystallization and hosting grown crystals. We found that IL-HCMs affect the selection mechanism of glucose isomerase (GI) polymorphs and make GI crystals grow completely immersed into the hydrogel layer. X-ray diffraction studies show that IL ions do not bind to the protein, likely because IL molecules are constrained in the polymeric framework. Our GI crystal structures have been compared with many existing GI crystal structures using multivariate analysis tools, allowing a comprehensive overview of factors determining structural similarities, i.e., temperature variations and external stresses exerted during or after crystal growth, such as dehydration or presence of hydrogel of a different nature. GI crystals grown on IL-HCM fit perfectly in this framework, showing typical features induced by external forces. Overall, protein crystallization by IL-HCMs show potential for biotechnological applications, as it could constitute a natural means for containing crystallized enzymes in working conditions. | |
Daniel Passos da Silva Michael L. Matwichuk, Delaney Townsend Courtney Reichhardt Doriano Lamba Daniel Wozniak & Matthew Parsek O J R The Pseudomonas aeruginosa lectin LecB binds to the exopolysaccharide Psl and stabilizes the biofilm matrix Journal Article Nature Communications, 10 , pp. 2183, 2019. @article{daSilva2019, title = {The Pseudomonas aeruginosa lectin LecB binds to the exopolysaccharide Psl and stabilizes the biofilm matrix}, author = {Daniel Passos da Silva, Michael L. Matwichuk, Delaney O. Townsend, Courtney Reichhardt, Doriano Lamba, Daniel J. Wozniak & Matthew R. Parsek}, doi = {10.1038/s41467-019-10201-4}, year = {2019}, date = {2019-05-16}, journal = {Nature Communications}, volume = {10}, pages = {2183}, abstract = {Pseudomonas aeruginosa biofilms are composed of exopolysaccharides (EPS), exogenous DNA, and proteins that hold these communities together. P. aeruginosa produces lectins LecA and LecB, which possess affinities towards sugars found in matrix EPS and mediate adherence of P. aeruginosa to target host cells. Here, we demonstrate that LecB binds to Psl, a key matrix EPS, and this leads to increased retention of both cells and EPS in a growing biofilm. This interaction is predicted to occur between the lectin and the branched side chains present on Psl. Finally, we show that LecB coordinates Psl localization in the biofilm. This constitutes a unique function for LecB and identifies it as a matrix protein that contributes to biofilm structure through EPS interactions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Pseudomonas aeruginosa biofilms are composed of exopolysaccharides (EPS), exogenous DNA, and proteins that hold these communities together. P. aeruginosa produces lectins LecA and LecB, which possess affinities towards sugars found in matrix EPS and mediate adherence of P. aeruginosa to target host cells. Here, we demonstrate that LecB binds to Psl, a key matrix EPS, and this leads to increased retention of both cells and EPS in a growing biofilm. This interaction is predicted to occur between the lectin and the branched side chains present on Psl. Finally, we show that LecB coordinates Psl localization in the biofilm. This constitutes a unique function for LecB and identifies it as a matrix protein that contributes to biofilm structure through EPS interactions. | |
Yang, Huaiyu; Belviso, Benny Danilo; Li, Xiaoyu; Chen, Wenqian; Mastropietro, Teresa Fina; Profio, Gianluca Di; Caliandro, Rocco; Heng, Jerry Y Y Optimization of Vapor Diffusion Conditions for Anti-CD20 Crystallization and Scale-Up to Meso Batch Journal Article Crystals, 9 (5), 2019, ISSN: 2073-4352. @article{cryst9050230, title = {Optimization of Vapor Diffusion Conditions for Anti-CD20 Crystallization and Scale-Up to Meso Batch}, author = { Huaiyu Yang and Benny Danilo Belviso and Xiaoyu Li and Wenqian Chen and Teresa Fina Mastropietro and Gianluca Di Profio and Rocco Caliandro and Jerry Y. Y. Heng}, url = {https://www.mdpi.com/2073-4352/9/5/230}, doi = {10.3390/cryst9050230}, issn = {2073-4352}, year = {2019}, date = {2019-04-29}, journal = {Crystals}, volume = {9}, number = {5}, abstract = {The crystal form is one of the preferred formulations for biotherapeutics, especially thanks to its ability to ensure high stability of the active ingredient. In addition, crystallization allows the recovery of a very pure drug, thus facilitating the manufacturing process. However, in many cases, crystallization is not trivial, and other formulations, such as the concentrate solution, represent the only choice. This is the case of anti-cluster of differentiation 20 (anti-CD20), which is one of the most sold antibodies for therapeutic uses. Here, we propose a set of optimized crystallization conditions for producing anti-CD20 needle-shaped crystals within 24 h in a very reproducible manner with high yield. High crystallization yield was obtained with high reproducibility using both hanging drop vapor diffusion and meso batch, which is a major step forward toward further scaling up the crystallization of anti-CD20. The influence of anti-CD20 storage conditions and the effect of different ions on the crystallization processes were also assessed. The crystal quality and the high yield allowed the first crystallographic investigation on anti-CD20, which positively confirmed the presence of the antibody in the crystals.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The crystal form is one of the preferred formulations for biotherapeutics, especially thanks to its ability to ensure high stability of the active ingredient. In addition, crystallization allows the recovery of a very pure drug, thus facilitating the manufacturing process. However, in many cases, crystallization is not trivial, and other formulations, such as the concentrate solution, represent the only choice. This is the case of anti-cluster of differentiation 20 (anti-CD20), which is one of the most sold antibodies for therapeutic uses. Here, we propose a set of optimized crystallization conditions for producing anti-CD20 needle-shaped crystals within 24 h in a very reproducible manner with high yield. High crystallization yield was obtained with high reproducibility using both hanging drop vapor diffusion and meso batch, which is a major step forward toward further scaling up the crystallization of anti-CD20. The influence of anti-CD20 storage conditions and the effect of different ions on the crystallization processes were also assessed. The crystal quality and the high yield allowed the first crystallographic investigation on anti-CD20, which positively confirmed the presence of the antibody in the crystals. | |
Chalupova, Katarina; Korabecny, Jan; Bartolini, Manuela; Monti, Barbara; Lamba, Doriano; Caliandro, Rosanna; Pesaresi, Alessandro; Brazzolotto, Xavier; Gastellier, Anne-Julie; Nachon, Florian; Pejchal, Jaroslav; Jarosova, Michaela; Hepnarova, Vendula; Jun, Daniel; Hrabinova, Martina; Dolezal, Rafael; Karasova, Jana Zdarova; Mzik, Martin; Kristofikova, Zdena; Misik, Jan; Muckova, Lubica; Jost, Petr; Soukup, Ondrej; Benkova, Marketa; Setnicka, Vladimir; Habartova, Lucie; Chvojkova, Marketa; Kleteckova, Lenka; Vales, Karel; Mezeiova, Eva; Uliassi, Elisa; Valis, Martin; Nepovimova, Eugenie; Bolognesi, Maria Laura; Kuca, Kamil Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease Journal Article European Journal of Medicinal Chemistry, 168 , pp. 491-514, 2019, ISSN: 0223-5234. @article{CHALUPOVA2019491, title = {Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease}, author = {Katarina Chalupova and Jan Korabecny and Manuela Bartolini and Barbara Monti and Doriano Lamba and Rosanna Caliandro and Alessandro Pesaresi and Xavier Brazzolotto and Anne-Julie Gastellier and Florian Nachon and Jaroslav Pejchal and Michaela Jarosova and Vendula Hepnarova and Daniel Jun and Martina Hrabinova and Rafael Dolezal and Jana Zdarova Karasova and Martin Mzik and Zdena Kristofikova and Jan Misik and Lubica Muckova and Petr Jost and Ondrej Soukup and Marketa Benkova and Vladimir Setnicka and Lucie Habartova and Marketa Chvojkova and Lenka Kleteckova and Karel Vales and Eva Mezeiova and Elisa Uliassi and Martin Valis and Eugenie Nepovimova and Maria Laura Bolognesi and Kamil Kuca}, doi = {10.1016/j.ejmech.2019.02.021}, issn = {0223-5234}, year = {2019}, date = {2019-04-15}, journal = {European Journal of Medicinal Chemistry}, volume = {168}, pages = {491-514}, abstract = {A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC50 values of 6.3 and 9.1 nM, respectively. For all the tacrine-tryptophan heterodimers, favorable inhibitory effect on hAChE as well as on hBChE was coined to the optimal spacer length ranging from five to eight carbon atoms between these two pharmacophores. S-K1035 also showed good ability to inhibit Aβ42 self-aggregation (58.6 ± 5.1% at 50 μM) as well as hAChE-induced Aβ40 aggregation (48.3 ± 6.3% at 100 μM). The X-ray crystallographic analysis of TcAChE in complex with S-K1035 pinpointed the utility of the hybridization strategy applied and the structures determined with the two K1035 enantiomers in complex with hBChE could explain the higher inhibition potency of S-K1035. Other in vitro evaluations predicted the ability of S-K1035 to cross blood-brain barrier and to exert a moderate inhibition potency against neuronal nitric oxide synthase. Based on the initial promising biochemical data and a safer in vivo toxicity compared to tacrine, S-K1035 was administered to scopolamine-treated rats being able to dose-dependently revert amnesia.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC50 values of 6.3 and 9.1 nM, respectively. For all the tacrine-tryptophan heterodimers, favorable inhibitory effect on hAChE as well as on hBChE was coined to the optimal spacer length ranging from five to eight carbon atoms between these two pharmacophores. S-K1035 also showed good ability to inhibit Aβ42 self-aggregation (58.6 ± 5.1% at 50 μM) as well as hAChE-induced Aβ40 aggregation (48.3 ± 6.3% at 100 μM). The X-ray crystallographic analysis of TcAChE in complex with S-K1035 pinpointed the utility of the hybridization strategy applied and the structures determined with the two K1035 enantiomers in complex with hBChE could explain the higher inhibition potency of S-K1035. Other in vitro evaluations predicted the ability of S-K1035 to cross blood-brain barrier and to exert a moderate inhibition potency against neuronal nitric oxide synthase. Based on the initial promising biochemical data and a safer in vivo toxicity compared to tacrine, S-K1035 was administered to scopolamine-treated rats being able to dose-dependently revert amnesia. | |
Daniela Russo Maya Dimova Lambreva, Christiane Alba Simionesco Pierre Sebban GiuseppinaRea Dynamics Properties of Photosynthetic Microorganisms Probed by Incoherent Neutron Scattering Journal Article Biophysical Journal, 116 (9), pp. 1759 - 1768, 2019. @article{Russo2019, title = {Dynamics Properties of Photosynthetic Microorganisms Probed by Incoherent Neutron Scattering}, author = {Daniela Russo, Maya Dimova Lambreva, Christiane Alba Simionesco, Pierre Sebban, GiuseppinaRea}, doi = {10.1016/j.bpj.2019.03.029}, year = {2019}, date = {2019-04-02}, journal = {Biophysical Journal}, volume = {116}, number = {9}, pages = {1759 - 1768}, abstract = {Studies on the dynamical properties of photosynthetic membranes of land plants and purple bacteria have been previously performed by neutron spectroscopy, revealing a tight coupling between specific photochemical reactions and macromolecular dynamics. Here, we probed the intrinsic dynamics of biotechnologically useful mutants of the green alga Chlamydomonas reinhardtii by incoherent neutron scattering coupled with prompt chlorophyll fluorescence experiments. We brought to light that single amino acid replacements in the plastoquinone (PQ)-binding niche of the photosystem II D1 protein impair electron transport (ET) efficiency between quinones and confer increased flexibility to the host membranes, expanding to the entire cells. Hence, a more flexible environment in the PQ-binding niche has been associated to a less efficient ET. A similar function/dynamics relationship was also demonstrated in Rhodobacter sphaeroides reaction centers having inhibited ET, indicating that flexibility at the quinones region plays a crucial role in evolutionarily distant organisms. Instead, a different functional/dynamical correlation was observed in algal mutants hosting a single amino acid replacement residing in a D1 domain far from the PQ-binding niche. Noteworthy, this mutant displayed the highest degree of flexibility, and besides having a nativelike ET efficiency in physiological conditions, it acquired novel, to our knowledge, phenotypic traits enabling it to preserve a high maximal quantum yield of photosystem II photochemistry in extreme habitats. Overall, in the nanosecond timescale, the degree of the observed flexibility is related to the mutation site; in the picosecond timescale, we highlighted the presence of a more pronounced dynamic heterogeneity in all mutants compared to the native cells, which could be related to a marked chemically heterogeneous environment.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Studies on the dynamical properties of photosynthetic membranes of land plants and purple bacteria have been previously performed by neutron spectroscopy, revealing a tight coupling between specific photochemical reactions and macromolecular dynamics. Here, we probed the intrinsic dynamics of biotechnologically useful mutants of the green alga Chlamydomonas reinhardtii by incoherent neutron scattering coupled with prompt chlorophyll fluorescence experiments. We brought to light that single amino acid replacements in the plastoquinone (PQ)-binding niche of the photosystem II D1 protein impair electron transport (ET) efficiency between quinones and confer increased flexibility to the host membranes, expanding to the entire cells. Hence, a more flexible environment in the PQ-binding niche has been associated to a less efficient ET. A similar function/dynamics relationship was also demonstrated in Rhodobacter sphaeroides reaction centers having inhibited ET, indicating that flexibility at the quinones region plays a crucial role in evolutionarily distant organisms. Instead, a different functional/dynamical correlation was observed in algal mutants hosting a single amino acid replacement residing in a D1 domain far from the PQ-binding niche. Noteworthy, this mutant displayed the highest degree of flexibility, and besides having a nativelike ET efficiency in physiological conditions, it acquired novel, to our knowledge, phenotypic traits enabling it to preserve a high maximal quantum yield of photosystem II photochemistry in extreme habitats. Overall, in the nanosecond timescale, the degree of the observed flexibility is related to the mutation site; in the picosecond timescale, we highlighted the presence of a more pronounced dynamic heterogeneity in all mutants compared to the native cells, which could be related to a marked chemically heterogeneous environment. | |
Migliaccio, Ludovico ; Manini, Paola ; Altamura, Davide ; Giannini, Cinzia ; Tassini, Paolo ; Maglione, Maria Grazia ; Minarini, Carla ; Pezzella, Alessandro Evidence of Unprecedented High Electronic Conductivity in Mammalian Pigment Based Eumelanin Thin Films After Thermal Annealing in Vacuum Journal Article Frontiers in Chemistry, 7 , pp. 162, 2019, ISSN: 2296-2646. @article{10.3389/fchem.2019.00162, title = {Evidence of Unprecedented High Electronic Conductivity in Mammalian Pigment Based Eumelanin Thin Films After Thermal Annealing in Vacuum}, author = {Migliaccio, Ludovico and Manini, Paola and Altamura, Davide and Giannini, Cinzia and Tassini, Paolo and Maglione, Maria Grazia and Minarini, Carla and Pezzella, Alessandro}, doi = {10.3389/fchem.2019.00162}, issn = {2296-2646}, year = {2019}, date = {2019-03-26}, journal = {Frontiers in Chemistry}, volume = {7}, pages = {162}, abstract = {Melanin denotes a variety of mammalian pigments, including the dark electrically conductive eumelanin and the reddish, sulfur-containing, pheomelanin. Organic (bio)electronics is showing increasing interests in eumelanin exploitation, e.g., for bio-interfaces, but the low conductivity of the material is limiting the development of eumelanin-based devices. Here, for the first time, we report an abrupt increase of the eumelanin electrical conductivity, revealing the highest value presented to date of 318 S/cm. This result, obtained via simple thermal annealing in vacuum of the material, designed on the base of the knowledge of the eumelanin chemical properties, also discloses the actual electronic nature of this material's conduction.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Melanin denotes a variety of mammalian pigments, including the dark electrically conductive eumelanin and the reddish, sulfur-containing, pheomelanin. Organic (bio)electronics is showing increasing interests in eumelanin exploitation, e.g., for bio-interfaces, but the low conductivity of the material is limiting the development of eumelanin-based devices. Here, for the first time, we report an abrupt increase of the eumelanin electrical conductivity, revealing the highest value presented to date of 318 S/cm. This result, obtained via simple thermal annealing in vacuum of the material, designed on the base of the knowledge of the eumelanin chemical properties, also discloses the actual electronic nature of this material's conduction. | |
Manna, Sara La; Roviello, Valentina; Scognamiglio, Pasqualina Liana; Diaferia, Carlo; Giannini, Cinzia; Sibillano, Teresa; Morelli, Giancarlo; Novellino, Ettore; Marasco, Daniela Amyloid fibers deriving from the aromatic core of C-terminal domain of nucleophosmin 1 Journal Article International Journal of Biological Macromolecules, 122 , pp. 517 - 525, 2019, ISSN: 0141-8130. @article{LAMANNA2019517, title = {Amyloid fibers deriving from the aromatic core of C-terminal domain of nucleophosmin 1}, author = {Sara La Manna and Valentina Roviello and Pasqualina Liana Scognamiglio and Carlo Diaferia and Cinzia Giannini and Teresa Sibillano and Giancarlo Morelli and Ettore Novellino and Daniela Marasco}, url = {http://www.sciencedirect.com/science/article/pii/S0141813018342004}, doi = {10.1016/j.ijbiomac.2018.10.210}, issn = {0141-8130}, year = {2019}, date = {2019-02-01}, journal = {International Journal of Biological Macromolecules}, volume = {122}, pages = {517 - 525}, abstract = {Nucleophosmin (NPM1) is the most frequently mutated gene in Acute Myeloid Leukemia (AML) patients and mutations lead to its aberrant cytoplasmatic accumulation in leukemic cells. Its C-terminal domain (CTD) is endowed with a globular structure consisting of a three-helix bundle in the wild type form that is disrupted by AML mutations. Our recent results demonstrate, unexpectedly and unequivocally, that regions of the CTD of NPM1 are prone to aggregate to amyloid states. Here we present novel studies, at solution as well as fibrillar states of a nonapeptide covering the 264\textendash272 region of NPM1: this small fragment is the most amyloidogenic stretch of the entire protein and its conformational and aggregation properties were investigated through Circular Dichroism, Fluorescence spectroscopies, amyloid seeding assay (ASA), isothermal titration calorimetry (ITC) and electrospray ionization (ESI) mass analyses. Structural features of fibrils were investigated by means of Scanning Electron Microscopy (SEM) and Wide-Angle X-ray Scattering (WAXS). This study deepens the amyloid fibrillization process of a short stretch of the CTD likely involved in the propagative mechanism for NPMc+ cytoplasmatic accumulation in leukemogenesis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Nucleophosmin (NPM1) is the most frequently mutated gene in Acute Myeloid Leukemia (AML) patients and mutations lead to its aberrant cytoplasmatic accumulation in leukemic cells. Its C-terminal domain (CTD) is endowed with a globular structure consisting of a three-helix bundle in the wild type form that is disrupted by AML mutations. Our recent results demonstrate, unexpectedly and unequivocally, that regions of the CTD of NPM1 are prone to aggregate to amyloid states. Here we present novel studies, at solution as well as fibrillar states of a nonapeptide covering the 264–272 region of NPM1: this small fragment is the most amyloidogenic stretch of the entire protein and its conformational and aggregation properties were investigated through Circular Dichroism, Fluorescence spectroscopies, amyloid seeding assay (ASA), isothermal titration calorimetry (ITC) and electrospray ionization (ESI) mass analyses. Structural features of fibrils were investigated by means of Scanning Electron Microscopy (SEM) and Wide-Angle X-ray Scattering (WAXS). This study deepens the amyloid fibrillization process of a short stretch of the CTD likely involved in the propagative mechanism for NPMc+ cytoplasmatic accumulation in leukemogenesis. | |
Leonelli, Francesca; Trombetta, Andrea; Bella', Angela 'La; Lucarelli, Giulio; Demitri, Nicola; Lamba, Doriano; Migneco, Luisa Maria; Bettolo, Rinaldo European Journal of Organic Chemistry, 2019 (7), pp. 1594-1599, 2019. @article{Leonelli2019, title = {Enantioselective Synthesis and X-ray Structure of (+)((4aS,5S,8aS)-5,8a-Dimethyl-7-methyleneoctahydro-2H-spiro[naphthalene-1,2′-[1,3]dioxolan]-5-yl)methyl-4-iodobenzoate}, author = {Francesca Leonelli and Andrea Trombetta and Angela 'La Bella' and Giulio Lucarelli and Nicola Demitri and Doriano Lamba and Luisa Maria Migneco and Rinaldo Bettolo}, url = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejoc.201801771}, doi = {10.1002/ejoc.201801771}, year = {2019}, date = {2019-01-03}, journal = {European Journal of Organic Chemistry}, volume = {2019}, number = {7}, pages = {1594-1599}, abstract = {The d and l amino acid mediated enantioselective intramolecular aldol reaction of 4-((1-methyl-2,6-dioxo-cyclohexyl)methyl)-pent-4-enal 1 leading, after dehydration, to (-)-(R) and (+)-(S) 4a-methyl-3-methylene-5-oxo-2,3,4,4a,5,6,7,8-octahydro-naphthalene-1-carbaldehyde 2 was explored. It was found that (-)-(R) carbaldehyde 2 is enantioselectively formed in the presence of l-amino acids while (+)-(S) carbaldehyde 2 is enantioselectively formed in the presence of d-amino acids. (-)-(R) Carbaldehyde 2 was then transformed into (+)-22. The absolute configuration and relative stereochemistry of the latter was established by single-crystal X-ray diffraction analysis of p-iodobenzoate (+)-23.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The d and l amino acid mediated enantioselective intramolecular aldol reaction of 4-((1-methyl-2,6-dioxo-cyclohexyl)methyl)-pent-4-enal 1 leading, after dehydration, to (-)-(R) and (+)-(S) 4a-methyl-3-methylene-5-oxo-2,3,4,4a,5,6,7,8-octahydro-naphthalene-1-carbaldehyde 2 was explored. It was found that (-)-(R) carbaldehyde 2 is enantioselectively formed in the presence of l-amino acids while (+)-(S) carbaldehyde 2 is enantioselectively formed in the presence of d-amino acids. (-)-(R) Carbaldehyde 2 was then transformed into (+)-22. The absolute configuration and relative stereochemistry of the latter was established by single-crystal X-ray diffraction analysis of p-iodobenzoate (+)-23. | |
Yan, Robert; Yalinca, Havva; Paoletti, Francesca; Gobbo, Francesco; Marchetti, Laura; Kuzmanic, Antonija; Lamba, Doriano; Gervasio, Francesco Luigi; Konarev, Petr V; Cattaneo, Antonino; Pastore, Annalisa The Structure of the Pro-domain of Mouse proNGF in Contact with the NGF Domain Journal Article Structure, 27 (1), pp. 78 - 89.e3, 2019, ISSN: 0969-2126. @article{YAN201978, title = {The Structure of the Pro-domain of Mouse proNGF in Contact with the NGF Domain}, author = {Robert Yan and Havva Yalinca and Francesca Paoletti and Francesco Gobbo and Laura Marchetti and Antonija Kuzmanic and Doriano Lamba and Francesco Luigi Gervasio and Petr V Konarev and Antonino Cattaneo and Annalisa Pastore}, url = {http://www.sciencedirect.com/science/article/pii/S0969212618303605}, doi = {10.1016/j.str.2018.09.013}, issn = {0969-2126}, year = {2019}, date = {2019-01-01}, journal = {Structure}, volume = {27}, number = {1}, pages = {78 - 89.e3}, abstract = {Summary Nerve growth factor (NGF) is an important neurotrophic factor involved in the regulation of cell differentiation and survival of target neurons. Expressed as a proNGF precursor, NGF is matured by furin-mediated protease cleavage. Increasing evidence suggests that NGF and proNGF have distinct functional roles. While the structure of mature NGF is available, little is known about that of the pro-domain because of its dynamical structural features. We exploited an ad hoc hybrid strategy based on nuclear magnetic resonance and modeling validated by small-angle X-ray scattering to gain novel insights on the pro-domain, both in isolation and in the context of proNGF. We show that the isolated pro-domain is intrinsically unstructured but forms transient intramolecular contacts with mature NGF and has per se the ability to induce growth cone collapse, indicating functional independence. Our data represent an important step toward the structural and functional characterization of the properties of proNGF.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Summary Nerve growth factor (NGF) is an important neurotrophic factor involved in the regulation of cell differentiation and survival of target neurons. Expressed as a proNGF precursor, NGF is matured by furin-mediated protease cleavage. Increasing evidence suggests that NGF and proNGF have distinct functional roles. While the structure of mature NGF is available, little is known about that of the pro-domain because of its dynamical structural features. We exploited an ad hoc hybrid strategy based on nuclear magnetic resonance and modeling validated by small-angle X-ray scattering to gain novel insights on the pro-domain, both in isolation and in the context of proNGF. We show that the isolated pro-domain is intrinsically unstructured but forms transient intramolecular contacts with mature NGF and has per se the ability to induce growth cone collapse, indicating functional independence. Our data represent an important step toward the structural and functional characterization of the properties of proNGF. | |
Faiella, Giuliana; Simonetti, Marco; D'Uffizi, Antonio; Tipo, Vincenzo; Cesarelli, Mario; Clemente, Fabrizio Use of Modelling Simulation to Monitor the Performance of a Pediatric Emergency Department Inproceedings Lhotska, Lenka; Sukupova, Lucie; ć, Igor Lackovi; Ibbott, Geoffrey S (Ed.): World Congress on Medical Physics and Biomedical Engineering 2018, pp. 567–572, Springer Singapore, Singapore, 2019, ISBN: 978-981-10-9035-6. @inproceedings{10.1007/978-981-10-9035-6_105, title = {Use of Modelling Simulation to Monitor the Performance of a Pediatric Emergency Department}, author = {Giuliana Faiella and Marco Simonetti and Antonio D'Uffizi and Vincenzo Tipo and Mario Cesarelli and Fabrizio Clemente}, editor = {Lenka Lhotska and Lucie Sukupova and Igor Lackovi{\'{c}} and Geoffrey S Ibbott}, url = {https://link.springer.com/chapter/10.1007%2F978-981-10-9035-6_105}, doi = {10.1007/978-981-10-9035-6_105}, isbn = {978-981-10-9035-6}, year = {2019}, date = {2019-01-01}, booktitle = {World Congress on Medical Physics and Biomedical Engineering 2018}, pages = {567--572}, publisher = {Springer Singapore}, address = {Singapore}, abstract = {Hospitals are complex systems in which different departments interact with each other. Systemic analytical models use systematic representations to facilitate the understanding of a complex process. The models are simulated with an imitation of the operations of a system and its internal processes, usually over time, and in appropriate detail. Simulation is used to study the performance of new systems as well as predict the effect of changes. Since Emergency Departments (ED) are unpredictable and frontline of healthcare service delivery, their detailed description and analysis are highly needed in order to design improvement actions. In this study, we will present the simulation of the ED a pediatric hospital which admits more than 100 k/year patients. The simulation tool is SIMIO®.}, keywords = {}, pubstate = {published}, tppubtype = {inproceedings} } Hospitals are complex systems in which different departments interact with each other. Systemic analytical models use systematic representations to facilitate the understanding of a complex process. The models are simulated with an imitation of the operations of a system and its internal processes, usually over time, and in appropriate detail. Simulation is used to study the performance of new systems as well as predict the effect of changes. Since Emergency Departments (ED) are unpredictable and frontline of healthcare service delivery, their detailed description and analysis are highly needed in order to design improvement actions. In this study, we will present the simulation of the ED a pediatric hospital which admits more than 100 k/year patients. The simulation tool is SIMIO®. | |
2018 |
|
Gijsbers, Abril; Montagut, Diana Carolina; Méndez-Godoy, Alfonso; Altamura, Davide; Saviano, Michele; Siliqi, Dritan; Sánchez-Puig, Nuria Interaction of the GTPase Elongation Factor Like-1 with the Shwachman-Diamond Syndrome Protein and Its Missense Mutations Journal Article International Journal of Molecular Sciences, 19 (12), 2018, ISSN: 1422-0067. @article{ijms19124012, title = {Interaction of the GTPase Elongation Factor Like-1 with the Shwachman-Diamond Syndrome Protein and Its Missense Mutations}, author = {Abril Gijsbers and Diana Carolina Montagut and Alfonso M\'{e}ndez-Godoy and Davide Altamura and Michele Saviano and Dritan Siliqi and Nuria S\'{a}nchez-Puig}, url = {http://www.mdpi.com/1422-0067/19/12/4012}, doi = {10.3390/ijms19124012}, issn = {1422-0067}, year = {2018}, date = {2018-12-12}, journal = {International Journal of Molecular Sciences}, volume = {19}, number = {12}, abstract = {The Shwachman-Diamond Syndrome (SDS) is a disorder arising from mutations in the genes encoding for the Shwachman-Bodian-Diamond Syndrome (SBDS) protein and the GTPase known as Elongation Factor Like-1 (EFL1). Together, these proteins remove the anti-association factor eIF6 from the surface of the pre-60S ribosomal subunit to promote the formation of mature ribosomes. SBDS missense mutations can either destabilize the protein fold or affect surface epitopes. The molecular alterations resulting from the latter remain largely unknown, although some evidence suggest that binding to EFL1 may be affected. We further explored the effect of these SBDS mutations on the interaction with EFL1, and showed that all tested mutations disrupted the binding to EFL1. Binding was either severely weakened or almost abolished, depending on the assessed mutation. In higher eukaryotes, SBDS is essential for development, and lack of the protein results in early lethality. The existence of patients whose only source of SBDS consists of that with surface missense mutations highlights the importance of the interaction with EFL1 for their function. Additionally, we studied the interaction mechanism of the proteins in solution and demonstrated that binding consists of two independent and cooperative events, with domains 2–3 of SBDS directing the initial interaction with EFL1, followed by docking of domain 1. In solution, both proteins exhibited large flexibility and consisted of an ensemble of conformations, as demonstrated by Small Angle X-ray Scattering (SAXS) experiments.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Shwachman-Diamond Syndrome (SDS) is a disorder arising from mutations in the genes encoding for the Shwachman-Bodian-Diamond Syndrome (SBDS) protein and the GTPase known as Elongation Factor Like-1 (EFL1). Together, these proteins remove the anti-association factor eIF6 from the surface of the pre-60S ribosomal subunit to promote the formation of mature ribosomes. SBDS missense mutations can either destabilize the protein fold or affect surface epitopes. The molecular alterations resulting from the latter remain largely unknown, although some evidence suggest that binding to EFL1 may be affected. We further explored the effect of these SBDS mutations on the interaction with EFL1, and showed that all tested mutations disrupted the binding to EFL1. Binding was either severely weakened or almost abolished, depending on the assessed mutation. In higher eukaryotes, SBDS is essential for development, and lack of the protein results in early lethality. The existence of patients whose only source of SBDS consists of that with surface missense mutations highlights the importance of the interaction with EFL1 for their function. Additionally, we studied the interaction mechanism of the proteins in solution and demonstrated that binding consists of two independent and cooperative events, with domains 2–3 of SBDS directing the initial interaction with EFL1, followed by docking of domain 1. In solution, both proteins exhibited large flexibility and consisted of an ensemble of conformations, as demonstrated by Small Angle X-ray Scattering (SAXS) experiments. | |
Italiano, Francesca; Agostiano, Angela; Belviso, Benny Danilo; Caliandro, Rocco; Carrozzini, Benedetta; Comparelli, Roberto; Melillo, Maria Teresa; Mesto, Ernesto; Tempesta, Gioacchino; Trotta, Massimo Colloids and Surfaces B: Biointerfaces, 172 , pp. 362 - 371, 2018, ISSN: 0927-7765. @article{ITALIANO2018362, title = {Interaction between the photosynthetic anoxygenic microorganism Rhodobacter sphaeroides and soluble gold compounds. From toxicity to gold nanoparticle synthesis}, author = {Francesca Italiano and Angela Agostiano and Benny Danilo Belviso and Rocco Caliandro and Benedetta Carrozzini and Roberto Comparelli and Maria Teresa Melillo and Ernesto Mesto and Gioacchino Tempesta and Massimo Trotta}, url = {http://www.sciencedirect.com/science/article/pii/S0927776518303813}, doi = {https://doi.org/10.1016/j.colsurfb.2018.06.010}, issn = {0927-7765}, year = {2018}, date = {2018-12-01}, journal = {Colloids and Surfaces B: Biointerfaces}, volume = {172}, pages = {362 - 371}, abstract = {Biological processes using microorganisms for nanoparticle synthesis are appealing as eco-friendly nanofactories. The response of the photosynthetic bacterium Rhodobacter sphaeroides to gold exposure and its reducing capability of Au(III) to produce stable gold nanoparticles (AuNPs), using metabolically active bacteria and quiescent biomass, is reported in this study. In the former case, bacterial cells were grown in presence of gold chloride at physiological pH. Gold exposure was found to cause a significant increase of the lag-phase duration at concentrations higher than 10 μM, suggesting the involvement of a resistance mechanism activated by Au(III). Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy/Energy Dispersive X-ray Spectrometry (SEM/EDS) analysis of bacterial cells confirmed the extracellular formation of AuNPs. Further studies were carried out on metabolically quiescent biomass incubated with gold chloride solution. The biosynthesized AuNPs were spherical in shape with an average size of 10 ± 3 nm, as analysed by Transmission Electron Microscopy (TEM). The nanoparticles were hydrophilic and stable against aggregation for several months. In order to identify the functional groups responsible for the reduction and stabilization of nanoparticles, AuNPs were analysed by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy, X-ray Photoelectron Spectroscopy (XPS), X-ray Fluorescence Spectrometry (XRF) and X-ray Absorption Spectroscopy (XAS) measurements. The obtained results indicate that gold ions bind to functional groups of cell membrane and are subsequently reduced by reducing sugars to gold nanoparticles and capped by a protein/peptide coat. Gold nanoparticles demonstrated to be efficient homogeneous catalysts in the degradation of nitroaromatic compounds.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Biological processes using microorganisms for nanoparticle synthesis are appealing as eco-friendly nanofactories. The response of the photosynthetic bacterium Rhodobacter sphaeroides to gold exposure and its reducing capability of Au(III) to produce stable gold nanoparticles (AuNPs), using metabolically active bacteria and quiescent biomass, is reported in this study. In the former case, bacterial cells were grown in presence of gold chloride at physiological pH. Gold exposure was found to cause a significant increase of the lag-phase duration at concentrations higher than 10 μM, suggesting the involvement of a resistance mechanism activated by Au(III). Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy/Energy Dispersive X-ray Spectrometry (SEM/EDS) analysis of bacterial cells confirmed the extracellular formation of AuNPs. Further studies were carried out on metabolically quiescent biomass incubated with gold chloride solution. The biosynthesized AuNPs were spherical in shape with an average size of 10 ± 3 nm, as analysed by Transmission Electron Microscopy (TEM). The nanoparticles were hydrophilic and stable against aggregation for several months. In order to identify the functional groups responsible for the reduction and stabilization of nanoparticles, AuNPs were analysed by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy, X-ray Photoelectron Spectroscopy (XPS), X-ray Fluorescence Spectrometry (XRF) and X-ray Absorption Spectroscopy (XAS) measurements. The obtained results indicate that gold ions bind to functional groups of cell membrane and are subsequently reduced by reducing sugars to gold nanoparticles and capped by a protein/peptide coat. Gold nanoparticles demonstrated to be efficient homogeneous catalysts in the degradation of nitroaromatic compounds. | |
Carlino, Elvio; Scattarella, Francesco; Caro, Liberato De; Giannini, Cinzia; Siliqi, Dritan; Colombo, Alessandro; Galli, Davide Emilio Coherent Diffraction Imaging in Transmission Electron Microscopy for Atomic Resolution Quantitative Studies of the Matter Journal Article Materials, 11 (11), 2018, ISSN: 1996-1944. @article{ma11112323, title = {Coherent Diffraction Imaging in Transmission Electron Microscopy for Atomic Resolution Quantitative Studies of the Matter}, author = {Elvio Carlino and Francesco Scattarella and Liberato De Caro and Cinzia Giannini and Dritan Siliqi and Alessandro Colombo and Davide Emilio Galli}, url = {http://www.mdpi.com/1996-1944/11/11/2323}, doi = {10.3390/ma11112323}, issn = {1996-1944}, year = {2018}, date = {2018-11-19}, journal = {Materials}, volume = {11}, number = {11}, abstract = {The paper focuses on the development of electron coherent diffraction imaging in transmission electron microscopy, made in the, approximately, last ten years in our collaborative research group, to study the properties of materials at atomic resolution, overcoming the limitations due to the aberrations of the electron lenses and obtaining atomic resolution images, in which the distribution of the maxima is directly related to the specimen atomic potentials projected onto the microscope image detector. Here, it is shown how augmented coherent diffraction imaging makes it possible to achieve quantitative atomic resolution maps of the specimen atomic species, even in the presence of low atomic number atoms within a crystal matrix containing heavy atoms. This aim is achieved by: (i) tailoring the experimental set-up, (ii) improving the experimental data by properly treating parasitic diffused intensities to maximize the measure of the significant information, (iii) developing efficient methods to merge the information acquired in both direct and reciprocal spaces, (iv) treating the dynamical diffused intensities to accurately measure the specimen projected potentials, (v) improving the phase retrieval algorithms to better explore the space of solutions. Finally, some of the future perspectives of coherent diffraction imaging in a transmission electron microscope are given.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The paper focuses on the development of electron coherent diffraction imaging in transmission electron microscopy, made in the, approximately, last ten years in our collaborative research group, to study the properties of materials at atomic resolution, overcoming the limitations due to the aberrations of the electron lenses and obtaining atomic resolution images, in which the distribution of the maxima is directly related to the specimen atomic potentials projected onto the microscope image detector. Here, it is shown how augmented coherent diffraction imaging makes it possible to achieve quantitative atomic resolution maps of the specimen atomic species, even in the presence of low atomic number atoms within a crystal matrix containing heavy atoms. This aim is achieved by: (i) tailoring the experimental set-up, (ii) improving the experimental data by properly treating parasitic diffused intensities to maximize the measure of the significant information, (iii) developing efficient methods to merge the information acquired in both direct and reciprocal spaces, (iv) treating the dynamical diffused intensities to accurately measure the specimen projected potentials, (v) improving the phase retrieval algorithms to better explore the space of solutions. Finally, some of the future perspectives of coherent diffraction imaging in a transmission electron microscope are given. | |
Coscia, Ubaldo; Ambrosone, Giuseppina; Palomba, Mariano; Binetti, Simona; Donne, Alessia Le; Siliqi, Dritan; Carotenuto, Gianfranco Photoconductivity of tellurium-poly(methyl methacrylate) in the ultraviolet–visible-near infrared range Journal Article Applied Surface Science, 457 , pp. 229 - 234, 2018, ISSN: 0169-4332. @article{COSCIA2018229, title = {Photoconductivity of tellurium-poly(methyl methacrylate) in the ultraviolet\textendashvisible-near infrared range}, author = {Ubaldo Coscia and Giuseppina Ambrosone and Mariano Palomba and Simona Binetti and Alessia Le Donne and Dritan Siliqi and Gianfranco Carotenuto}, url = {http://www.sciencedirect.com/science/article/pii/S0169433218317896}, doi = {https://doi.org/10.1016/j.apsusc.2018.06.221}, issn = {0169-4332}, year = {2018}, date = {2018-11-01}, journal = {Applied Surface Science}, volume = {457}, pages = {229 - 234}, abstract = {Fine powders composed of tellurium grains of average size <10 nm were produced by dry vibration milling combined with liquid-phase sedimentation techniques, starting from polycrystalline powders with average grain diameter of ca. 30 μm. Nanocomposite films were obtained by binding the nanosized tellurium grains with poly(methyl methacrylate). Raman spectroscopy revealed that the films were based on the coexistence of tellurium and tellurium oxide crystalline phases due to a partial oxidation in air of the grains. The optical measurements of the fabricated material showed that the absorbance was nearly constant in the 310\textendash2200 nm range and that a typical UV absorption peak of the nanostructured tellurium was centered at around 260 nm. An extensive characterization of the photoconductivity properties was carried out by illuminating the tellurium-poly(methyl methacrylate) films with white light or radiations of different spectral composition selected from the UV\textendashVis-NIR region. Data analysis has allowed to demonstrate that the photoresponse is closely related to the optical absorption and is independent of the spectral composition of the incident radiation in the wavelength range from 310 to 2200 nm, while the photocurrent increases linearly as a function of the optical power density over about three orders of magnitude.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Fine powders composed of tellurium grains of average size <10 nm were produced by dry vibration milling combined with liquid-phase sedimentation techniques, starting from polycrystalline powders with average grain diameter of ca. 30 μm. Nanocomposite films were obtained by binding the nanosized tellurium grains with poly(methyl methacrylate). Raman spectroscopy revealed that the films were based on the coexistence of tellurium and tellurium oxide crystalline phases due to a partial oxidation in air of the grains. The optical measurements of the fabricated material showed that the absorbance was nearly constant in the 310–2200 nm range and that a typical UV absorption peak of the nanostructured tellurium was centered at around 260 nm. An extensive characterization of the photoconductivity properties was carried out by illuminating the tellurium-poly(methyl methacrylate) films with white light or radiations of different spectral composition selected from the UV–Vis-NIR region. Data analysis has allowed to demonstrate that the photoresponse is closely related to the optical absorption and is independent of the spectral composition of the incident radiation in the wavelength range from 310 to 2200 nm, while the photocurrent increases linearly as a function of the optical power density over about three orders of magnitude. | |