Look at a list of IC publications: 2020, 2019, 2018, 2017, 2016, 2015, 2014
2020 |
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Antonacci, Amina; Celso, Fabrizio Lo; Barone, Giampaolo; Calandra, Pietro; Grunenberg, Jörg; Moccia, Maria; Gatto, Emanuela; Giardi, Maria Teresa; Scognamiglio, Viviana Novel atrazine-binding biomimetics inspired to the D1 protein from the photosystem II of Chlamydomonas reinhardtii Journal Article International Journal of Biological Macromolecules, 163 , pp. 817 - 823, 2020, ISSN: 0141-8130. @article{ANTONACCI2020817, title = {Novel atrazine-binding biomimetics inspired to the D1 protein from the photosystem II of Chlamydomonas reinhardtii}, author = {Amina Antonacci and Fabrizio Lo Celso and Giampaolo Barone and Pietro Calandra and J\"{o}rg Grunenberg and Maria Moccia and Emanuela Gatto and Maria Teresa Giardi and Viviana Scognamiglio}, url = {http://www.sciencedirect.com/science/article/pii/S0141813020337533}, doi = {10.1016/j.ijbiomac.2020.07.010}, issn = {0141-8130}, year = {2020}, date = {2020-11-15}, journal = {International Journal of Biological Macromolecules}, volume = {163}, pages = {817 - 823}, abstract = {Biomimetic design represents an emerging field for improving knowledge of natural molecules, as well as to project novel artificial tools with specific functions for biosensing. Effective strategies have been exploited to design artificial bioreceptors, taking inspiration from complex supramolecular assemblies. Among them, size-minimization strategy sounds promising to provide bioreceptors with tuned sensitivity, stability, and selectivity, through the ad hoc manipulation of chemical species at the molecular scale. Herein, a novel biomimetic peptide enabling herbicide binding was designed bioinspired to the D1 protein of the Photosystem II of the green alga Chlamydomonas reinhardtii. The D1 protein portion corresponding to the QB plastoquinone binding niche is capable of interacting with photosynthetic herbicides. A 50-mer peptide in the region of D1 protein from the residue 211 to 280 was designed in silico, and molecular dynamic simulations were performed alone and in complex with atrazine. An equilibrated structure was obtained with a stable pocked for atrazine binding by three H-bonds with SER222, ASN247, and HIS272 residues. Computational data were confirmed by fluorescence spectroscopy and circular dichroism on the peptide obtained by automated synthesis. Atrazine binding at nanomolar concentrations was followed by fluorescence spectroscopy, highlighting peptide suitability for optical sensing of herbicides at safety limits.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Biomimetic design represents an emerging field for improving knowledge of natural molecules, as well as to project novel artificial tools with specific functions for biosensing. Effective strategies have been exploited to design artificial bioreceptors, taking inspiration from complex supramolecular assemblies. Among them, size-minimization strategy sounds promising to provide bioreceptors with tuned sensitivity, stability, and selectivity, through the ad hoc manipulation of chemical species at the molecular scale. Herein, a novel biomimetic peptide enabling herbicide binding was designed bioinspired to the D1 protein of the Photosystem II of the green alga Chlamydomonas reinhardtii. The D1 protein portion corresponding to the QB plastoquinone binding niche is capable of interacting with photosynthetic herbicides. A 50-mer peptide in the region of D1 protein from the residue 211 to 280 was designed in silico, and molecular dynamic simulations were performed alone and in complex with atrazine. An equilibrated structure was obtained with a stable pocked for atrazine binding by three H-bonds with SER222, ASN247, and HIS272 residues. Computational data were confirmed by fluorescence spectroscopy and circular dichroism on the peptide obtained by automated synthesis. Atrazine binding at nanomolar concentrations was followed by fluorescence spectroscopy, highlighting peptide suitability for optical sensing of herbicides at safety limits. | |
Romanucci, Valeria; García-Viñuales, Sara; Tempra, Carmelo; Bernini, Roberta; Zarrelli, Armando; Lolicato, Fabio; Milardi, Danilo; Fabio, Giovanni Di Modulating Aβ aggregation by tyrosol-based ligands: The crucial role of the catechol moiety Journal Article Biophysical Chemistry, 265 , pp. 106434, 2020, ISSN: 0301-4622. @article{ROMANUCCI2020106434, title = {Modulating Aβ aggregation by tyrosol-based ligands: The crucial role of the catechol moiety}, author = {Valeria Romanucci and Sara Garc\'{i}a-Vi\~{n}uales and Carmelo Tempra and Roberta Bernini and Armando Zarrelli and Fabio Lolicato and Danilo Milardi and Giovanni Di Fabio}, url = {http://www.sciencedirect.com/science/article/pii/S0301462220301423}, doi = {10.1016/j.bpc.2020.106434}, issn = {0301-4622}, year = {2020}, date = {2020-10-01}, journal = {Biophysical Chemistry}, volume = {265}, pages = {106434}, abstract = {The abnormal deposition of Aβ amyloid deposits in the brain is a hallmark of Alzheimer's disease (AD). Based on this evidence, many current therapeutic approaches focus on the development of small molecules halting Aβ aggregation. However, due to the temporary and elusive structures of amyloid assemblies, the rational design of aggregation inhibitors remains a challenging task. Here we combine ThT assays and MD simulations to study Aβ aggregation in the presence of the natural compounds tyrosol (TY), 3-hydroxytyrosol (HDT), and 3-methoxytyrosol (homovanillyl alcohol - HVA). We show that albeit HDT is a potent inhibitor of amyloid growth, TY and HVA catalyze fibril formation. An inspection of MD simulations trajectories revealed that the different effects of these three molecules on Aβ1\textendash40 aggregation are ascribable to their capacity to arrange H-bonds network between the ligand (position C-3) and the peptide (Glu22). We believe that our results may contribute to the design of more effective and safe small molecules able to contrast pathogenic amyloid aggregation}, keywords = {}, pubstate = {published}, tppubtype = {article} } The abnormal deposition of Aβ amyloid deposits in the brain is a hallmark of Alzheimer's disease (AD). Based on this evidence, many current therapeutic approaches focus on the development of small molecules halting Aβ aggregation. However, due to the temporary and elusive structures of amyloid assemblies, the rational design of aggregation inhibitors remains a challenging task. Here we combine ThT assays and MD simulations to study Aβ aggregation in the presence of the natural compounds tyrosol (TY), 3-hydroxytyrosol (HDT), and 3-methoxytyrosol (homovanillyl alcohol - HVA). We show that albeit HDT is a potent inhibitor of amyloid growth, TY and HVA catalyze fibril formation. An inspection of MD simulations trajectories revealed that the different effects of these three molecules on Aβ1–40 aggregation are ascribable to their capacity to arrange H-bonds network between the ligand (position C-3) and the peptide (Glu22). We believe that our results may contribute to the design of more effective and safe small molecules able to contrast pathogenic amyloid aggregation | |
Tundo, G R; Sbardella, D; Santoro, A M; Coletta, A; Oddone, F; Grasso, G; Milardi, D; Lacal, P M; Marini, S; Purrello, R; Graziani, G; Coletta, M The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges Journal Article Pharmacology & Therapeutics, 213 , pp. 107579, 2020, ISSN: 0163-7258. @article{TUNDO2020107579, title = {The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges}, author = {G R Tundo and D Sbardella and A M Santoro and A Coletta and F Oddone and G Grasso and D Milardi and P M Lacal and S Marini and R Purrello and G Graziani and M Coletta}, url = {http://www.sciencedirect.com/science/article/pii/S0163725820301078}, doi = {10.1016/j.pharmthera.2020.107579}, issn = {0163-7258}, year = {2020}, date = {2020-09-01}, journal = {Pharmacology & Therapeutics}, volume = {213}, pages = {107579}, keywords = {}, pubstate = {published}, tppubtype = {article} } | |
Moro, Giulia; Bottari, Fabio; Liberi, Stefano; Covaceuszach, Sonia; Cassetta, Alberto; Angelini, Alessandro; Wael, Karolien De; Moretto, Ligia Maria Bioelectrochemistry, 134 , pp. 107540, 2020, ISSN: 1567-5394. @article{MORO2020107540, title = {Covalent immobilization of delipidated human serum albumin on poly(pyrrole-2-carboxylic) acid film for the impedimetric detection of perfluorooctanoic acid}, author = {Giulia Moro and Fabio Bottari and Stefano Liberi and Sonia Covaceuszach and Alberto Cassetta and Alessandro Angelini and Karolien De Wael and Ligia Maria Moretto}, url = {http://www.sciencedirect.com/science/article/pii/S1567539420301201}, doi = {10.1016/j.bioelechem.2020.107540}, issn = {1567-5394}, year = {2020}, date = {2020-08-01}, journal = {Bioelectrochemistry}, volume = {134}, pages = {107540}, abstract = {The immobilization of biomolecules at screen printed electrodes for biosensing applications is still an open challenge. To enrich the toolbox of bioelectrochemists, graphite screen printed electrodes (G-SPE) were modified with an electropolymerized film of pyrrole-2-carboxilic acid (Py-2-COOH), a pyrrole derivative rich in carboxylic acid functional groups. These functionalities are suitable for the covalent immobilization of biomolecular recognition layers. The electropolymerization was first optimized to obtain stable and conductive polymeric films, comparing two different electrolytes: sodium dodecyl sulphate (SDS) and sodium perchlorate. The G-SPE modified with Py-2-COOH in 0.1 M SDS solution showed the required properties and were further tested. A proof-of-concept study for the development of an impedimetric sensor for perfluorooctanoic acid (PFOA) was carried out using the delipidated human serum albumin (hSA) as bioreceptor. The data interpretation was supported by size exclusion chromatography and small-angle X-ray scattering (SEC-SAXS) analysis of the bioreceptor-target complex and the preliminary results suggest the possibility to further develop this biosensing strategy for toxicological and analytical studies.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The immobilization of biomolecules at screen printed electrodes for biosensing applications is still an open challenge. To enrich the toolbox of bioelectrochemists, graphite screen printed electrodes (G-SPE) were modified with an electropolymerized film of pyrrole-2-carboxilic acid (Py-2-COOH), a pyrrole derivative rich in carboxylic acid functional groups. These functionalities are suitable for the covalent immobilization of biomolecular recognition layers. The electropolymerization was first optimized to obtain stable and conductive polymeric films, comparing two different electrolytes: sodium dodecyl sulphate (SDS) and sodium perchlorate. The G-SPE modified with Py-2-COOH in 0.1 M SDS solution showed the required properties and were further tested. A proof-of-concept study for the development of an impedimetric sensor for perfluorooctanoic acid (PFOA) was carried out using the delipidated human serum albumin (hSA) as bioreceptor. The data interpretation was supported by size exclusion chromatography and small-angle X-ray scattering (SEC-SAXS) analysis of the bioreceptor-target complex and the preliminary results suggest the possibility to further develop this biosensing strategy for toxicological and analytical studies. | |
Krokidis, Marios G; D’Errico, Mariarosaria; Pascucci, Barbara; Parlanti, Eleonora; Masi, Annalisa; Ferreri, Carla; Chatgilialoglu, Chryssostomos Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells Journal Article Cells, 9 (7), pp. 1671, 2020. @article{krokidis2020oxygen, title = {Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells}, author = {Marios G Krokidis and Mariarosaria D’Errico and Barbara Pascucci and Eleonora Parlanti and Annalisa Masi and Carla Ferreri and Chryssostomos Chatgilialoglu}, doi = {10.3390/cells9071671}, year = {2020}, date = {2020-07-11}, journal = {Cells}, volume = {9}, number = {7}, pages = {1671}, publisher = {Multidisciplinary Digital Publishing Institute}, abstract = {Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%). In particular, the four 5′,8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. cPu levels were found comparable to 8-oxo-Pu in all cases (3\textendash6 lesions/106 nucleotides), slightly increasing on going from hyperoxia to physioxia to hypoxia. Moreover, higher levels of four cPu were observed under hypoxia in both CSA and CSB-defective cells as compared to normal counterparts, along with a significant enhancement of 8-oxo-Pu. These findings revealed that exposure to different oxygen tensions induced oxidative DNA damage in CS cells, repairable by NER or base excision repair (BER) pathways. In NER-defective CS patients, these results support the hypothesis that the clinical neurological features might be connected to the accumulation of cPu. Moreover, the elimination of dysfunctional mitochondria in CS cells is associated with a reduction in the oxidative DNA damage.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%). In particular, the four 5′,8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. cPu levels were found comparable to 8-oxo-Pu in all cases (3–6 lesions/106 nucleotides), slightly increasing on going from hyperoxia to physioxia to hypoxia. Moreover, higher levels of four cPu were observed under hypoxia in both CSA and CSB-defective cells as compared to normal counterparts, along with a significant enhancement of 8-oxo-Pu. These findings revealed that exposure to different oxygen tensions induced oxidative DNA damage in CS cells, repairable by NER or base excision repair (BER) pathways. In NER-defective CS patients, these results support the hypothesis that the clinical neurological features might be connected to the accumulation of cPu. Moreover, the elimination of dysfunctional mitochondria in CS cells is associated with a reduction in the oxidative DNA damage. | |
Arduini, Fabiana; Micheli, Laura; Scognamiglio, Viviana; Mazzaracchio, Vincenzo; Moscone, Danila Sustainable materials for the design of forefront printed (bio)sensors applied in agrifood sector Journal Article TrAC Trends in Analytical Chemistry, 128 , pp. 115909, 2020, ISSN: 0165-9936. @article{ARDUINI2020115909, title = {Sustainable materials for the design of forefront printed (bio)sensors applied in agrifood sector}, author = {Fabiana Arduini and Laura Micheli and Viviana Scognamiglio and Vincenzo Mazzaracchio and Danila Moscone}, url = {http://www.sciencedirect.com/science/article/pii/S0165993620301382}, doi = {10.1016/j.trac.2020.115909}, issn = {0165-9936}, year = {2020}, date = {2020-07-01}, journal = {TrAC Trends in Analytical Chemistry}, volume = {128}, pages = {115909}, abstract = {The search for sustainability has now become a duty for all those entities, nations or people who intend to combat poverty in the world, safeguard the environment and bridge the gap of disparities that unfortunately still exist between underdeveloped countries and medium-high developed nations. The agrifood sector plays an important role in this vision, and the development of sustainable analytical devices at low cost and easy to use for everyone, suitable for being adopted by those countries whose technological development does not allow them to take up expensive and sophisticated laboratory techniques, may constitute a contribution towards achieving the objectives listed above. In this review we illustrate some examples of electrochemical devices realized utilizing sustainable materials, such as paper, as support for disposable and reagent-free (bio)sensors applied to the monitoring of food quality and safety. We also mention the first applications of new carbonaceous materials obtained from the recycling of agrifood waste products, which promise interesting features for electrochemical applications.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The search for sustainability has now become a duty for all those entities, nations or people who intend to combat poverty in the world, safeguard the environment and bridge the gap of disparities that unfortunately still exist between underdeveloped countries and medium-high developed nations. The agrifood sector plays an important role in this vision, and the development of sustainable analytical devices at low cost and easy to use for everyone, suitable for being adopted by those countries whose technological development does not allow them to take up expensive and sophisticated laboratory techniques, may constitute a contribution towards achieving the objectives listed above. In this review we illustrate some examples of electrochemical devices realized utilizing sustainable materials, such as paper, as support for disposable and reagent-free (bio)sensors applied to the monitoring of food quality and safety. We also mention the first applications of new carbonaceous materials obtained from the recycling of agrifood waste products, which promise interesting features for electrochemical applications. | |
Masi, Andrea; Alvani, Carlo; Armenio, Achille Angrisani; Augieri, Andrea; Barba, Luisa; Campi, Gaetano; Celentano, Giuseppe; Chita, Giuseppe; Fabbri, Fabio; Zignani, Chiarasole Fiamozzi; Barbera, Aurelio La; Piperno, Laura; Rizzo, Francesco; Rufoloni, Alessandro; Silva, Enrico; Vannozzi, Angelo; Varsano, Francesca Fe(Se,Te) from melting routes: the influence of thermal processing on microstructure and superconducting properties Journal Article Superconductor Science and Technology, 33 (8), pp. 084007, 2020. @article{Masi_2020, title = {Fe(Se,Te) from melting routes: the influence of thermal processing on microstructure and superconducting properties}, author = {Andrea Masi and Carlo Alvani and Achille Angrisani Armenio and Andrea Augieri and Luisa Barba and Gaetano Campi and Giuseppe Celentano and Giuseppe Chita and Fabio Fabbri and Chiarasole Fiamozzi Zignani and Aurelio La Barbera and Laura Piperno and Francesco Rizzo and Alessandro Rufoloni and Enrico Silva and Angelo Vannozzi and Francesca Varsano}, url = {https://doi.org/10.1088%2F1361-6668%2Fab9acf}, doi = {10.1088/1361-6668/ab9acf}, year = {2020}, date = {2020-07-01}, journal = {Superconductor Science and Technology}, volume = {33}, number = {8}, pages = {084007}, publisher = {IOP Publishing}, abstract = {Superconducting properties of the Fe(Se,Te) system are directly related to its microstructure. However, in the framework of a not well assessed phase diagram, a large spread of chemico-physical and functional properties is reported for compounds characterized by similar overall chemical compositions. This is in particular observed in materials produced by melting routes, where chemical inhomogeneities and multiple phases are commonly obtained. Both composition and morphology of these inhomogeneities seem to play a role in the behaviour of the superconducting phases, pointing out the need to assess the dependence of phase composition and therefore of the material performance on the sample thermal history. In this work, the effect of different post-synthesis annealing treatments is studied. A melting route has been adopted to synthesize polycrystalline samples, subsequently subjected to thermal treatments at different temperatures. Morphology and microstructure were characterized by means of x-ray diffraction and microscopy techniques. The superconducting properties have been evaluated by means of electrical and magnetic measurements. It is observed how microstructure, chemical composition and morphology of the obtained products strictly depend on the annealing temperature. Moreover, a crucial role of the cooling step is evidenced: in fact, a rapid cooling procedure from high temperature leads to the formation of high temperature (Tc onset > 19 K) superconducting phases, but the overall bulk superconducting performance is negatively affected. Other annealing treatments can promote instead an enhancement in the critical current at high fields with respect to pristine sample, suggesting that a careful engineering of a post-synthesis thermal step can represent a useful tool to optimize the material properties.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Superconducting properties of the Fe(Se,Te) system are directly related to its microstructure. However, in the framework of a not well assessed phase diagram, a large spread of chemico-physical and functional properties is reported for compounds characterized by similar overall chemical compositions. This is in particular observed in materials produced by melting routes, where chemical inhomogeneities and multiple phases are commonly obtained. Both composition and morphology of these inhomogeneities seem to play a role in the behaviour of the superconducting phases, pointing out the need to assess the dependence of phase composition and therefore of the material performance on the sample thermal history. In this work, the effect of different post-synthesis annealing treatments is studied. A melting route has been adopted to synthesize polycrystalline samples, subsequently subjected to thermal treatments at different temperatures. Morphology and microstructure were characterized by means of x-ray diffraction and microscopy techniques. The superconducting properties have been evaluated by means of electrical and magnetic measurements. It is observed how microstructure, chemical composition and morphology of the obtained products strictly depend on the annealing temperature. Moreover, a crucial role of the cooling step is evidenced: in fact, a rapid cooling procedure from high temperature leads to the formation of high temperature (Tc onset > 19 K) superconducting phases, but the overall bulk superconducting performance is negatively affected. Other annealing treatments can promote instead an enhancement in the critical current at high fields with respect to pristine sample, suggesting that a careful engineering of a post-synthesis thermal step can represent a useful tool to optimize the material properties. | |
Masi, Annalisa; Fortini, Paola; Krokidis, Marios G; Romeo, Erminia Francesca; Bascietto, Cinzia; De Angelis, Paola ; Guglielmi, Valeria; Chatgilialoglu, Chryssostomos Increased levels of 5′,8-Cyclopurine DNA lesions in inflammatory bowel diseases Journal Article Redox Biology, 34 , pp. 101562, 2020, ISSN: 2213-2317. @article{MASI2020101562b, title = {Increased levels of 5′,8-Cyclopurine DNA lesions in inflammatory bowel diseases}, author = {Annalisa Masi and Paola Fortini and Marios G. Krokidis and Erminia Francesca Romeo and Cinzia Bascietto and Paola {De Angelis} and Valeria Guglielmi and Chryssostomos Chatgilialoglu}, url = {http://www.sciencedirect.com/science/article/pii/S2213231720303712}, doi = {10.1016/j.redox.2020.101562}, issn = {2213-2317}, year = {2020}, date = {2020-07-01}, journal = {Redox Biology}, volume = {34}, pages = {101562}, abstract = {Chronic inflammation is estimated to be a causative factor in a variety of diseases. Under inflammatory conditions reactive oxygen species (ROS) and nitrogen species (RNS) are released leading to DNA damage accumulation and genomic instability. Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are oxidative DNA lesions, exclusively derived from the attack of HO• radicals, which are known to have cytotoxic and mutagenic properties. Herein, we have analyzed the presence of cPu in genomic DNA isolated from fresh colon and visceral adipose tissue biopsies collected from inflammatory bowel diseases (IBD)-affected patients and severely obese subjects, respectively, versus what observed in the control specimens. In colon biopsies, characterized by a higher gene expression level of inducible nitric oxide synthase (iNOS), a significant increase of 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dA) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) lesions and an accumulation of both diastereomeric cPu have been detected. In contrast, the 8-oxo-dA and 8-oxo-dG levels were extremely lower compared to the colon tissues values and no accumulation of cPu, in the inflamed visceral adipose tissue biopsies isolated from bariatric patients versus the lean counterpart was reported. In addition, in adipose tissue undetectable levels of iNOS have been found. These data suggest a potential involvement of cPu in the colon cancer susceptibility observed in IBD patients.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Chronic inflammation is estimated to be a causative factor in a variety of diseases. Under inflammatory conditions reactive oxygen species (ROS) and nitrogen species (RNS) are released leading to DNA damage accumulation and genomic instability. Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are oxidative DNA lesions, exclusively derived from the attack of HO• radicals, which are known to have cytotoxic and mutagenic properties. Herein, we have analyzed the presence of cPu in genomic DNA isolated from fresh colon and visceral adipose tissue biopsies collected from inflammatory bowel diseases (IBD)-affected patients and severely obese subjects, respectively, versus what observed in the control specimens. In colon biopsies, characterized by a higher gene expression level of inducible nitric oxide synthase (iNOS), a significant increase of 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dA) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) lesions and an accumulation of both diastereomeric cPu have been detected. In contrast, the 8-oxo-dA and 8-oxo-dG levels were extremely lower compared to the colon tissues values and no accumulation of cPu, in the inflamed visceral adipose tissue biopsies isolated from bariatric patients versus the lean counterpart was reported. In addition, in adipose tissue undetectable levels of iNOS have been found. These data suggest a potential involvement of cPu in the colon cancer susceptibility observed in IBD patients. | |
Sbardella, Diego; Coletta, Andrea; Tundo, Grazia Raffaella; Ahmed, Ikhlas M M; Bellia, Francesco; Oddone, Francesco; Manni, Gianluca; Coletta, Massimo Biochemical Pharmacology, 177 , pp. 113977, 2020, ISSN: 0006-2952. @article{SBARDELLA2020113977, title = {Structural and functional evidence for citicoline binding and modulation of 20S proteasome activity: Novel insights into its pro-proteostatic effect}, author = {Diego Sbardella and Andrea Coletta and Grazia Raffaella Tundo and Ikhlas M M Ahmed and Francesco Bellia and Francesco Oddone and Gianluca Manni and Massimo Coletta}, url = {http://www.sciencedirect.com/science/article/pii/S0006295220302057}, doi = {10.1016/j.bcp.2020.113977}, issn = {0006-2952}, year = {2020}, date = {2020-07-01}, journal = {Biochemical Pharmacology}, volume = {177}, pages = {113977}, abstract = {Citicoline or CDP-choline is a drug, made up by a cytidine 5′-diphosphate moiety and choline, which upon adsorption is rapidly hydrolyzed into cytidine 5′-diphosphate and choline, easily bypassing the blood\textendashbrain barrier. Once in the brain, these metabolites are used to re-synthesize citicoline in neurons and in the other cell histo-types which uptake them. Citicoline administration finds broad therapeutic application in the treatment of glaucoma as well as other retinal disorders by virtue of its safety profile and neuro-protective and neuroenhancer activity, which significantly improves the visual function. Further, though supported by limited clinical studies, this molecule finds therapeutic application in neurodegenerative disease, delaying the cognitive decline in Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) subjects. In this work we show that citicoline greatly affects the proteolytic activity of the 20S proteasome on synthetic and natural substrates, functioning as a bimodal allosteric modulator, likely binding at multiple sites. In silico binding simulations identify several potential binding sites for citicoline on 20S proteasome, and their topology envisages the possibility that, by occupying some of these pockets, citicoline may induce a conformational shift of the 20S proteasome, allowing to sketch a working hypothesis for the structural basis of its function as allosteric modulator. In addition, we show that over the same concentration range citicoline affects the distribution of assembled proteasome populations and turn-over of ubiquitinated proteins in SH-SY5Y and SK-N-BE human neuroblastoma cells, suggesting its potential role as a regulator of proteostasis in nervous cells.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Citicoline or CDP-choline is a drug, made up by a cytidine 5′-diphosphate moiety and choline, which upon adsorption is rapidly hydrolyzed into cytidine 5′-diphosphate and choline, easily bypassing the blood–brain barrier. Once in the brain, these metabolites are used to re-synthesize citicoline in neurons and in the other cell histo-types which uptake them. Citicoline administration finds broad therapeutic application in the treatment of glaucoma as well as other retinal disorders by virtue of its safety profile and neuro-protective and neuroenhancer activity, which significantly improves the visual function. Further, though supported by limited clinical studies, this molecule finds therapeutic application in neurodegenerative disease, delaying the cognitive decline in Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) subjects. In this work we show that citicoline greatly affects the proteolytic activity of the 20S proteasome on synthetic and natural substrates, functioning as a bimodal allosteric modulator, likely binding at multiple sites. In silico binding simulations identify several potential binding sites for citicoline on 20S proteasome, and their topology envisages the possibility that, by occupying some of these pockets, citicoline may induce a conformational shift of the 20S proteasome, allowing to sketch a working hypothesis for the structural basis of its function as allosteric modulator. In addition, we show that over the same concentration range citicoline affects the distribution of assembled proteasome populations and turn-over of ubiquitinated proteins in SH-SY5Y and SK-N-BE human neuroblastoma cells, suggesting its potential role as a regulator of proteostasis in nervous cells. | |
García-Viñuales, Sara; Ahmed, Rashik; Sciacca, Michele F M; Lanza, Valeria; Giuffrida, Maria Laura; Zimbone, Stefania; Romanucci, Valeria; Zarrelli, Armando; Bongiorno, Corrado; Spinella, Natalia; Galati, Clelia; Fabio, Giovanni Di; Melacini, Giuseppe; Milardi, Danilo Trehalose conjugates of silybin as prodrugs for targeting toxic Aβ aggregates Journal Article ACS Chemical Neuroscience, 0 (ja), pp. null, 2020. @article{doi:10.1021/acschemneuro.0c00232, title = {Trehalose conjugates of silybin as prodrugs for targeting toxic Aβ aggregates}, author = {Sara Garc\'{i}a-Vi\~{n}uales and Rashik Ahmed and Michele F M Sciacca and Valeria Lanza and Maria Laura Giuffrida and Stefania Zimbone and Valeria Romanucci and Armando Zarrelli and Corrado Bongiorno and Natalia Spinella and Clelia Galati and Giovanni Di Fabio and Giuseppe Melacini and Danilo Milardi}, doi = {10.1021/acschemneuro.0c00232}, year = {2020}, date = {2020-07-01}, journal = {ACS Chemical Neuroscience}, volume = {0}, number = {ja}, pages = {null}, abstract = {Alzheimer’s Disease (AD) is linked to the abnormal accumulation of amyloid β peptide (Aβ) in the brain. Silybin B, a natural compound extracted from milk thistle (Silibum marianum), has been shown to significantly inhibit Aβ aggregation in vitro and to exert neuroprotective properties in vivo. However, further explorations of silybin B’s clinical potential are currently limited by three main factors: (a) poor solubility; (b) instability in blood serum; (c) only partial knowledge of silybin’s mechanism of action. Here, we address these three limitations. We demonstrate that conjugation of a trehalose moiety to silybin significantly increases both water solubility and stability in blood serum without significantly compromising its anti-aggregation properties. Furthermore, using a combination of biophysical techniques with different spatial resolutions, i.e. TEM, ThT fluorescence, CD, and NMR spectroscopy, we profiled the interactions of the trehalose conjugate with both Aβ monomers and oligomers. Finally, the comparative analysis with silybin A, a less active diastereomer of silybin B, revealed how even subtle differences in chemical structure may entail significantly divergent effects on amyloid inhibition. The resulting insight on the mechanism of action of silybins as aggregation inhibitors is anticipated to facilitate the future investigation of silybin’s therapeutic potential.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Alzheimer’s Disease (AD) is linked to the abnormal accumulation of amyloid β peptide (Aβ) in the brain. Silybin B, a natural compound extracted from milk thistle (Silibum marianum), has been shown to significantly inhibit Aβ aggregation in vitro and to exert neuroprotective properties in vivo. However, further explorations of silybin B’s clinical potential are currently limited by three main factors: (a) poor solubility; (b) instability in blood serum; (c) only partial knowledge of silybin’s mechanism of action. Here, we address these three limitations. We demonstrate that conjugation of a trehalose moiety to silybin significantly increases both water solubility and stability in blood serum without significantly compromising its anti-aggregation properties. Furthermore, using a combination of biophysical techniques with different spatial resolutions, i.e. TEM, ThT fluorescence, CD, and NMR spectroscopy, we profiled the interactions of the trehalose conjugate with both Aβ monomers and oligomers. Finally, the comparative analysis with silybin A, a less active diastereomer of silybin B, revealed how even subtle differences in chemical structure may entail significantly divergent effects on amyloid inhibition. The resulting insight on the mechanism of action of silybins as aggregation inhibitors is anticipated to facilitate the future investigation of silybin’s therapeutic potential. | |
Sbardella, Diego; Tundo, Grazia Raffaella; Cunsolo, Vincenzo; Grasso, Giuseppe; Cascella, Raffaella; Caputo, Valerio; Santoro, Anna Maria; Milardi, Danilo; Pecorelli, Alessandra; Ciaccio, Chiara; Pierro, Donato Di; Leoncini, Silvia; Campagnolo, Luisa; Pironi, Virginia; Oddone, Francesco; Manni, Priscilla; Foti, Salvatore; Giardina, Emiliano; Felice, Claudio De; Hayek, Joussef; Curatolo, Paolo; Galasso, Cinzia; Valacchi, Giuseppe; Coletta, Massimiliano; Graziani, Grazia; Marini, Stefano Defective proteasome biogenesis into skin fibroblasts isolated from Rett syndrome subjects with MeCP2 non-sense mutations Journal Article Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1866 (7), pp. 165793, 2020, ISSN: 0925-4439. @article{SBARDELLA2020165793, title = {Defective proteasome biogenesis into skin fibroblasts isolated from Rett syndrome subjects with MeCP2 non-sense mutations}, author = {Diego Sbardella and Grazia Raffaella Tundo and Vincenzo Cunsolo and Giuseppe Grasso and Raffaella Cascella and Valerio Caputo and Anna Maria Santoro and Danilo Milardi and Alessandra Pecorelli and Chiara Ciaccio and Donato Di Pierro and Silvia Leoncini and Luisa Campagnolo and Virginia Pironi and Francesco Oddone and Priscilla Manni and Salvatore Foti and Emiliano Giardina and Claudio De Felice and Joussef Hayek and Paolo Curatolo and Cinzia Galasso and Giuseppe Valacchi and Massimiliano Coletta and Grazia Graziani and Stefano Marini}, url = {http://www.sciencedirect.com/science/article/pii/S0925443920301381}, doi = {10.1016/j.bbadis.2020.165793}, issn = {0925-4439}, year = {2020}, date = {2020-07-01}, journal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease}, volume = {1866}, number = {7}, pages = {165793}, abstract = {Rett Syndrome (RTT) is a rare X-linked neurodevelopmental disorder which affects about 1: 10000 live births. In >95% of subjects RTT is caused by a mutation in Methyl-CpG binding protein-2 (MECP2) gene, which encodes for a transcription regulator with pleiotropic genetic/epigenetic activities. The molecular mechanisms underscoring the phenotypic alteration of RTT are largely unknown and this has impaired the development of therapeutic approaches to alleviate signs and symptoms during disease progression. A defective proteasome biogenesis into two skin primary fibroblasts isolated from RTT subjects harbouring non-sense (early-truncating) MeCP2 mutations (i.e., R190fs and R255X) is herewith reported. Proteasome is the proteolytic machinery of Ubiquitin Proteasome System (UPS), a pathway of overwhelming relevance for post-mitotic cells metabolism. Molecular, transcription and proteomic analyses indicate that MeCP2 mutations down-regulate the expression of one proteasome subunit, α7, and of two chaperones, PAC1 and PAC2, which bind each other in the earliest step of proteasome biogenesis. Furthermore, this molecular alteration recapitulates in neuron-like SH-SY5Y cells upon silencing of MeCP2 expression, envisaging a general significance of this transcription regulator in proteasome biogenesis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Rett Syndrome (RTT) is a rare X-linked neurodevelopmental disorder which affects about 1: 10000 live births. In >95% of subjects RTT is caused by a mutation in Methyl-CpG binding protein-2 (MECP2) gene, which encodes for a transcription regulator with pleiotropic genetic/epigenetic activities. The molecular mechanisms underscoring the phenotypic alteration of RTT are largely unknown and this has impaired the development of therapeutic approaches to alleviate signs and symptoms during disease progression. A defective proteasome biogenesis into two skin primary fibroblasts isolated from RTT subjects harbouring non-sense (early-truncating) MeCP2 mutations (i.e., R190fs and R255X) is herewith reported. Proteasome is the proteolytic machinery of Ubiquitin Proteasome System (UPS), a pathway of overwhelming relevance for post-mitotic cells metabolism. Molecular, transcription and proteomic analyses indicate that MeCP2 mutations down-regulate the expression of one proteasome subunit, α7, and of two chaperones, PAC1 and PAC2, which bind each other in the earliest step of proteasome biogenesis. Furthermore, this molecular alteration recapitulates in neuron-like SH-SY5Y cells upon silencing of MeCP2 expression, envisaging a general significance of this transcription regulator in proteasome biogenesis. | |
Dibenedetto, Carlo Nazareno; Sibillano, Teresa; Brescia, Rosaria; Prato, Mirko; Triggiani, Leonardo; Giannini, Cinzia; Panniello, Annamaria; Corricelli, Michela; Comparelli, Roberto; Ingrosso, Chiara; Depalo, Nicoletta; Agostiano, Angela; Curri, Maria Lucia; Striccoli, Marinella; Fanizza, Elisabetta PbS Quantum Dots Decorating TiO2 Nanocrystals: Synthesis, Topology, and Optical Properties of the Colloidal Hybrid Architecture Journal Article Molecules, 25 (12), 2020, ISSN: 1420-3049. @article{molecules25122939, title = {PbS Quantum Dots Decorating TiO2 Nanocrystals: Synthesis, Topology, and Optical Properties of the Colloidal Hybrid Architecture}, author = {Carlo Nazareno Dibenedetto and Teresa Sibillano and Rosaria Brescia and Mirko Prato and Leonardo Triggiani and Cinzia Giannini and Annamaria Panniello and Michela Corricelli and Roberto Comparelli and Chiara Ingrosso and Nicoletta Depalo and Angela Agostiano and Maria Lucia Curri and Marinella Striccoli and Elisabetta Fanizza}, url = {https://www.mdpi.com/1420-3049/25/12/2939}, doi = {10.3390/molecules25122939}, issn = {1420-3049}, year = {2020}, date = {2020-06-26}, journal = {Molecules}, volume = {25}, number = {12}, abstract = {Fabrication of heterostructures by merging two or more materials in a single object. The domains at the nanoscale represent a viable strategy to purposely address materials’ properties for applications in several fields such as catalysis, biomedicine, and energy conversion. In this case, solution-phase seeded growth and the hot-injection method are ingeniously combined to fabricate TiO2/PbS heterostructures. The interest in such hybrid nanostructures arises from their absorption properties that make them advantageous candidates as solar cell materials for more efficient solar light harvesting and improved light conversion. Due to the strong lattice mismatch between TiO2 and PbS, the yield of the hybrid structure and the control over its properties are challenging. In this study, a systematic investigation of the heterostructure synthesis as a function of the experimental conditions (such as seeds’ surface chemistry, reaction temperature, and precursor concentration), its topology, structural properties, and optical properties are carried out. The morphological and chemical characterizations confirm the formation of small dots of PbS by decorating the oleylamine surface capped TiO2 nanocrystals under temperature control. Remarkably, structural characterization points out that the formation of heterostructures is accompanied by modification of the crystallinity of the TiO2 domain, which is mainly ascribed to lattice distortion. This result is also confirmed by photoluminescence spectroscopy, which shows intense emission in the visible range. This originated from self-trapped excitons, defects, and trap emissive states.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Fabrication of heterostructures by merging two or more materials in a single object. The domains at the nanoscale represent a viable strategy to purposely address materials’ properties for applications in several fields such as catalysis, biomedicine, and energy conversion. In this case, solution-phase seeded growth and the hot-injection method are ingeniously combined to fabricate TiO2/PbS heterostructures. The interest in such hybrid nanostructures arises from their absorption properties that make them advantageous candidates as solar cell materials for more efficient solar light harvesting and improved light conversion. Due to the strong lattice mismatch between TiO2 and PbS, the yield of the hybrid structure and the control over its properties are challenging. In this study, a systematic investigation of the heterostructure synthesis as a function of the experimental conditions (such as seeds’ surface chemistry, reaction temperature, and precursor concentration), its topology, structural properties, and optical properties are carried out. The morphological and chemical characterizations confirm the formation of small dots of PbS by decorating the oleylamine surface capped TiO2 nanocrystals under temperature control. Remarkably, structural characterization points out that the formation of heterostructures is accompanied by modification of the crystallinity of the TiO2 domain, which is mainly ascribed to lattice distortion. This result is also confirmed by photoluminescence spectroscopy, which shows intense emission in the visible range. This originated from self-trapped excitons, defects, and trap emissive states. | |
Magrì, Antonio; Tabbì, Giovanni; Natale, Giuseppe Di; Mendola, Diego La; Pietropaolo, Adriana; Zoroddu, Maria Antonietta; Peana, Massimiliano; Rizzarelli, Enrico Chemistry – A European Journal, n/a (n/a), 2020. @article{doi:10.1002/chem.202002114, title = {Zinc interactions with a soluble mutated rat amylin to mimic whole human amylin. An experimental and simulation approach to understand stoichiometry, speciation and coordination of the metal complexes}, author = {Antonio Magr\`{i} and Giovanni Tabb\`{i} and Giuseppe Di Natale and Diego La Mendola and Adriana Pietropaolo and Maria Antonietta Zoroddu and Massimiliano Peana and Enrico Rizzarelli}, url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202002114}, doi = {10.1002/chem.202002114}, year = {2020}, date = {2020-06-02}, journal = {Chemistry \textendash A European Journal}, volume = {n/a}, number = {n/a}, abstract = {Islet Amyloid Polypeptide (IAPP) is a hormone co-secreted with insulin and zinc from pancreatic β-cells. To overcome the low solubility of human IAPP, we characterized the zinc complexes species formed with: i) a mutated form of rat-IAPP(1-37;R18H) able to mimic the human IAPP; ii) the r-IAPP(1-37) and the IAPP(1-8) fragment. Stoichiometry, speciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometric and NMR-based measurements combined with DFT and free-energy simulations. Mononuclear species start to form around pH 6; Zn 2+ binds both His18 and N-amino terminus in rat-IAPP(1-37; R18H).The in silico study allows us to assess not only a structured turn compact domain in r-IAPP(1-37) and r-IAPP(1-37;R18H) featured by a different free energy barrier for the transition from the compact to elongated conformation upon the coordination of Zn 2+ but also to bring into light a coordination shell further stabilized by non-covalent interactions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Islet Amyloid Polypeptide (IAPP) is a hormone co-secreted with insulin and zinc from pancreatic β-cells. To overcome the low solubility of human IAPP, we characterized the zinc complexes species formed with: i) a mutated form of rat-IAPP(1-37;R18H) able to mimic the human IAPP; ii) the r-IAPP(1-37) and the IAPP(1-8) fragment. Stoichiometry, speciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometric and NMR-based measurements combined with DFT and free-energy simulations. Mononuclear species start to form around pH 6; Zn 2+ binds both His18 and N-amino terminus in rat-IAPP(1-37; R18H).The in silico study allows us to assess not only a structured turn compact domain in r-IAPP(1-37) and r-IAPP(1-37;R18H) featured by a different free energy barrier for the transition from the compact to elongated conformation upon the coordination of Zn 2+ but also to bring into light a coordination shell further stabilized by non-covalent interactions. | |
Cacciotti, Ilaria; Pallotto, Francesca; Scognamiglio, Viviana; Moscone, Danila; Arduini, Fabiana Materials Science and Engineering: C, 111 , pp. 110744, 2020, ISSN: 0928-4931. @article{CACCIOTTI2020110744, title = {Reusable optical multi-plate sensing system for pesticide detection by using electrospun membranes as smart support for acetylcholinesterase immobilisation}, author = {Ilaria Cacciotti and Francesca Pallotto and Viviana Scognamiglio and Danila Moscone and Fabiana Arduini}, url = {http://www.sciencedirect.com/science/article/pii/S0928493119310069}, doi = {10.1016/j.msec.2020.110744}, issn = {0928-4931}, year = {2020}, date = {2020-06-01}, journal = {Materials Science and Engineering: C}, volume = {111}, pages = {110744}, abstract = {Herein we report a multiplated and biopolymeric-based optical bioassay for organophosphate detection based on the use of acetylcholinesterase (AChE) as biocomponent and biopolymeric electrospun fibrous mats as eco-designed supports for AChE immobilisation. The principle of the detection relays on the decrease of enzymatic activity due to the capability of the organophosphorus pesticides to irreversibly inhibit AChE, which is optically detected using Ellman colorimetric method. The proposed bioassay consists in a novel, cost-effective, and multiplex-based 96-well system, in combination with customised biopolymeric membranes modified with AChE, with the aim to deliver a sustainable analytical tool. Indeed, the designed set-up should provide and guarantee several advantages, including: i) the re-use of plastic multi-plate with the only replacement of polymer dishes in the case of inhibition absence; ii) the exploiting of the properties of the immobilised enzyme, i.e. multiple analysis using the same amount of enzyme, reducing the AChE amount for analysis. In detail, three different biopolymers (i.e. polylactic acid (PLA), polycaprolactone (PCL), and poly-hydroxybutyrate-co-hydroxyvalerate (PHBV)) were investigated and morphologically characterised, as supports for enzyme immobilisation, to identify the optimal one. Among them, PHBV was selected as the best support to immobilise AChE by cross-linking method. The analytical features of the bioassay were then assessed by measuring standard solutions of paraoxon in a range of concentrations between 10 and 100 ppb, achieving a linear range up to 60 ppb and a detection limit of 10 ppb. Thus, the suitability of this sustainable bioassay to detect organophosphate at ppb level was demonstrated.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Herein we report a multiplated and biopolymeric-based optical bioassay for organophosphate detection based on the use of acetylcholinesterase (AChE) as biocomponent and biopolymeric electrospun fibrous mats as eco-designed supports for AChE immobilisation. The principle of the detection relays on the decrease of enzymatic activity due to the capability of the organophosphorus pesticides to irreversibly inhibit AChE, which is optically detected using Ellman colorimetric method. The proposed bioassay consists in a novel, cost-effective, and multiplex-based 96-well system, in combination with customised biopolymeric membranes modified with AChE, with the aim to deliver a sustainable analytical tool. Indeed, the designed set-up should provide and guarantee several advantages, including: i) the re-use of plastic multi-plate with the only replacement of polymer dishes in the case of inhibition absence; ii) the exploiting of the properties of the immobilised enzyme, i.e. multiple analysis using the same amount of enzyme, reducing the AChE amount for analysis. In detail, three different biopolymers (i.e. polylactic acid (PLA), polycaprolactone (PCL), and poly-hydroxybutyrate-co-hydroxyvalerate (PHBV)) were investigated and morphologically characterised, as supports for enzyme immobilisation, to identify the optimal one. Among them, PHBV was selected as the best support to immobilise AChE by cross-linking method. The analytical features of the bioassay were then assessed by measuring standard solutions of paraoxon in a range of concentrations between 10 and 100 ppb, achieving a linear range up to 60 ppb and a detection limit of 10 ppb. Thus, the suitability of this sustainable bioassay to detect organophosphate at ppb level was demonstrated. | |
Gioacchino, Michael Di; Bianconi, Antonio; Burghammer, Manfred; Ciasca, Gabriele; Bruni, Fabio; Campi, Gaetano Myelin basic protein dynamics from out-of-equilibrium functional state to degraded state in myelin Journal Article BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1862 (6), 2020, ISSN: 0005-2736. @article{ISI:000528195500021, title = {Myelin basic protein dynamics from out-of-equilibrium functional state to degraded state in myelin}, author = {Michael Di Gioacchino and Antonio Bianconi and Manfred Burghammer and Gabriele Ciasca and Fabio Bruni and Gaetano Campi}, doi = {10.1016/j.bbamem.2020.183256}, issn = {0005-2736}, year = {2020}, date = {2020-06-01}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES}, volume = {1862}, number = {6}, publisher = {ELSEVIER}, address = {RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS}, abstract = {Living matter is a quasi-stationary out-of-equilibrium system; in this physical condition, structural fluctuations at nano- and meso-scales are needed to understand the physics behind its biological functionality. Myelin has a simple ultrastructure whose fluctuations show correlated disorder in its functional out-of-equilibrium state. However, there is no information on the relationship between this correlated disorder and the dynamics of the intrinsically disordered Myelin Basic Protein (MBP) which is expected to influence the membrane structure and overall functionality. In this work, we have investigated the role of this protein structural dynamics in the myelin ultrastructure fluctuations in various conditions, by using synchrotron Scanning micro X Ray Diffraction and Small Angle X ray Scattering. We have induced the crossover from out-of-equilibrium functional state to in-equilibrium degeneration changing the pH to values far from physiological condition. The observed compression of the cytosolic layer thickness probes that the intrinsic large MBP fluctuations preserve the cytosol structure also in the degraded state. Thus, the transition of myelin ultrastructure from correlated to uncorrelated disordered state, is principally affected by the deformation of the membrane and extracellular domain.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Living matter is a quasi-stationary out-of-equilibrium system; in this physical condition, structural fluctuations at nano- and meso-scales are needed to understand the physics behind its biological functionality. Myelin has a simple ultrastructure whose fluctuations show correlated disorder in its functional out-of-equilibrium state. However, there is no information on the relationship between this correlated disorder and the dynamics of the intrinsically disordered Myelin Basic Protein (MBP) which is expected to influence the membrane structure and overall functionality. In this work, we have investigated the role of this protein structural dynamics in the myelin ultrastructure fluctuations in various conditions, by using synchrotron Scanning micro X Ray Diffraction and Small Angle X ray Scattering. We have induced the crossover from out-of-equilibrium functional state to in-equilibrium degeneration changing the pH to values far from physiological condition. The observed compression of the cytosolic layer thickness probes that the intrinsic large MBP fluctuations preserve the cytosol structure also in the degraded state. Thus, the transition of myelin ultrastructure from correlated to uncorrelated disordered state, is principally affected by the deformation of the membrane and extracellular domain. | |