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21.
Francesca Potenza Maria Concetta Cufaro Linda Di Biase Valeria Panella Antonella Di Campli Anna Giulia Ruggieri Beatrice Dufrusine Elena Restelli Laura Pietrangelo Feliciano Protasi Damiana Pieragostino Vincenzo De Laurenzi Luca Federici Roberto Chiesa Michele Sallese 《International journal of molecular sciences》2021,22(22)
Marinesco–Sjogren syndrome (MSS) is a rare multisystem pediatric disorder, caused by loss-of-function mutations in the gene encoding the endoplasmic reticulum cochaperone SIL1. SIL1 acts as a nucleotide exchange factor for BiP, which plays a central role in secretory protein folding. SIL1 mutant cells have reduced BiP-assisted protein folding, cannot fulfil their protein needs, and experience chronic activation of the unfolded protein response (UPR). Maladaptive UPR may explain the cerebellar and skeletal muscle degeneration responsible for the ataxia and muscle weakness typical of MSS. However, the cause of other more variable, clinical manifestations, such as mild to severe mental retardation, hypogonadism, short stature, and skeletal deformities, is less clear. To gain insights into the pathogenic mechanisms and/or adaptive responses to SIL1 loss, we carried out cell biological and proteomic investigations in skin fibroblasts derived from a young patient carrying the SIL1 R111X mutation. Despite fibroblasts not being overtly affected in MSS, we found morphological and biochemical changes indicative of UPR activation and altered cell metabolism. All the cell machineries involved in RNA splicing and translation were strongly downregulated, while protein degradation via lysosome-based structures was boosted, consistent with an attempt of the cell to reduce the workload of the endoplasmic reticulum and dispose of misfolded proteins. Cell metabolism was extensively affected as we observed a reduction in lipid synthesis, an increase in beta oxidation, and an enhancement of the tricarboxylic acid cycle, with upregulation of eight of its enzymes. Finally, the catabolic pathways of various amino acids, including valine, leucine, isoleucine, tryptophan, lysine, aspartate, and phenylalanine, were enhanced, while the biosynthetic pathways of arginine, serine, glycine, and cysteine were reduced. These results indicate that, in addition to UPR activation and increased protein degradation, MSS fibroblasts have profound metabolic alterations, which may help them cope with the absence of SIL1. 相似文献
22.
Gross A Besov A Reck DD Sorek S Ben-Dor G Britan A Palchikov E 《Environmental science & technology》2003,37(19):4481-4486
A theory developed suggested that significant displacement of solute in saturated porous media results from the propagation of compression waves. Four independent one-dimensional experimental setups and a variety of laboratory methods were used to confirm the predictions of the theory, specifically aimed at developing a novel method of inducing compression waves for use in remediation of contaminated aquifers. Compaction and shock waves were emitted through granular porous media saturated with saline water. The changes in solute concentration at observation points along the propagating wave were used to verify the validity of theory. The first setup was designed mainly to provide a qualitative assessment (i.e., changes in pressure due to the propagating wave were not recorded). In situ quantitative measurements of the pressure and electrical conductivity profiles along a sand column were done with the second and third experimental setups, respectively, to short and long shock waves. In the fourth setup, solute displacement was visualized by X-ray absorption. The findings were consistent with the theory in all experimental setups. 相似文献
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24.
Borschel C Spindler S Lerose D Bochmann A Christiansen SH Nietzsche S Oertel M Ronning C 《Nanotechnology》2011,22(18):185307
Ion beams can be used to permanently bend and re-align nanowires after growth. We have irradiated ZnO nanowires with energetic ions, achieving bending and alignment in different directions. Not only the bending of single nanowires is studied in detail, but also the simultaneous alignment of large ensembles of ZnO nanowires. Computer simulations reveal how the bending is initiated by ion beam induced damage. Detailed structural characterization identifies dislocations to relax stresses and make the bending and alignment permanent, even surviving annealing procedures. 相似文献
25.
Dieter Nickel Wolfgang Von Rybinski Eva-Maria Kutschmann Cosima Stubenrauch Gerhard H. Findenegg 《European Journal of Lipid Science and Technology》1996,98(11):363-369
The cleaning and washing power of surfactants is based on physicochemical effects. Of special importance is the emulsifying and dispersing capacity. While the emulsifying capacity describes the behaviour of two immiscible liquid phases, the dispersing capacity is a measure of how a liquid phase influences a solid phase. The interfacial tension is the most important parameter which characterizes the interaction between an aqueous surfactant solution and an oil. A quantitative evaluation of the affinity of a surfactant solution to a solid substrate occurs through the measurement of the absorbed quantities. A comparative discussion of the surfactant effect on both types of interfaces using the example of alkyl polyglycosides provides information about the property profile during the washing and cleaning process. 相似文献
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28.
Alexander Batista-Duharte Luis Sendra Maria Jos Herrero Deivys Leandro Portuondo Damiana Tllez-Martínez Gladys Olivera Manuel Fernndez-Delgado Beatriz Javega Guadalupe Herrera Alicia Martínez Paulo Inacio Costa Iracilda Zeppone Carlos Salvador Francisco Alio 《International journal of molecular sciences》2021,22(7)
Background: In recent years, there has been great interest in developing molecular adjuvants based on antisense oligonucleotides (ASOs) targeting immunosuppressor pathways with inhibitory effects on regulatory T cells (Tregs) to improve immunogenicity and vaccine efficacy. We aim to evaluate the immunostimulating effect of 2′OMe phosphorothioated Foxp3-targeted ASO in an antifungal adjuvanted recombinant vaccine. Methods: The uptake kinetics of Foxp3 ASO, its cytotoxicity and its ability to deplete Tregs were evaluated in murine splenocytes in vitro. Groups of mice were vaccinated with recombinant enolase (Eno) of Sporothix schenckii in Montanide Gel 01 adjuvant alone or in combination with either 1 µg or 8 µg of Foxp3 ASO. The titers of antigen-specific antibody in serum samples from vaccinated mice (male C57BL/6) were determined by ELISA (enzyme-linked immunosorbent assay). Cultured splenocytes from each group were activated in vitro with Eno and the levels of IFN-γ and IL-12 were also measured by ELISA. The results showed that the anti-Eno antibody titer was significantly higher upon addition of 8 µM Foxp3 ASO in the vaccine formulation compared to the standard vaccine without ASO. In vitro and in vivo experiments suggest that Foxp3 ASO enhances specific immune responses by means of Treg depletion during vaccination. Conclusion: Foxp3 ASO significantly enhances immune responses against co-delivered adjuvanted recombinant Eno vaccine and it has the potential to improve vaccine immunogenicity. 相似文献
29.
Damiana Pieragostino Michele D'Alessandro Maria di Ioia Carmine Di Ilio Paolo Sacchetta Piero Del Boccio 《Proteomics. Clinical applications》2015,9(1-2):169-186
Proteomics and metabolomics investigations of body fluids present several challenges for biomarker discovery of several diseases. The search for biomarkers is actually conducted in different body fluids, even if the ideal biomarker can be found in an easily accessible biological fluid, because, if validated, the biomarker could be sought in the healthy population. In this regard, tears could be considered an optimum material obtained by noninvasive procedures. In the past years, the scientific community has become more interested in the study of tears for the research of new biomarkers not only for ocular diseases. In this review, we provide a discussion on the current state of biomarkers research in tears and their relevance for clinical practice, and report the main results of clinical proteomics studies on systemic and eye diseases. We summarize the main methods for tear samples analyses and report recent advances in “omics” platforms for tears investigations. Moreover, we want to take stock of the emerging field of metabolomics and lipidomics as a new and integrated approach to study protein-metabolites interplay for biomarkers research, where tears represent a still unexplored and attractive field. 相似文献
30.
Anne Kessler Orquidéa Menéndez-Aguirre Jörg Hinrichs Cosima Stubenrauch Jochen Weiss 《Journal of dairy science》2013
In this study, the surface tension, miscibility, and particle size distribution of a solution containing an αs-casein (CN)-rich CN fraction (54 wt % αs-CN, 32 wt % β-CN, and 15 wt % κ-CN) were determined at pH 6.6. The nondialyzed CN fraction was compared with a dialyzed one. In the nondialyzed sample, every charge on the protein was compensated by 0.3 charges coming from counterions, whereas in the dialyzed sample, only 0.2 charges could be assigned to each charge on the protein. This relation was determined by calculating the charges at the proteins, taking the measured mineral content into account. The surface tension was measured as a function of the protein concentration by the du Noüy ring method at room temperature. Results indicated alterations in the surface properties after reduction of counterions. The equilibrium surface tension above the critical micelle concentration increased from 40.1 × 10−3 to 45 × 10−3 N/m, the critical micelle concentration increased from 0.9 × 10−4 to 2 × 10−3 mol/L, and the minimal area occupied per molecule at the surface increased from 2.4 × 10−18 to 4.6 × 10−18 m2. Cloud points were determined by measuring the absorbance of CN solutions as a function of the temperature. The cloud points were found to be concentration dependent and had a minimum at 0.2 wt % at 34°C for nondialyzed CN and at 0.25 wt % at 28°C for dialyzed CN, again demonstrating the influence of counterion reduction. Below the cloud point, a micellar phase was found to exist. The hydrodynamic diameter of the micelles were characterized by dynamic light scattering in both auto- and cross-correlation mode. However, no influence of reduction in counterions could be observed, possibly due to the fact that dynamic light scattering is not a suitable method for this type of system. The presence of self-assembled structures was verified by freeze-fracture electron microscopy. The observed differences between dialyzed and nondialyzed samples were explained by changes in the counterion cloud surrounding the proteins. Consequently, the electrostatic interactions between as well as within the CN are altered by dialysis, which, in turn, affects the behavior at the surface as well as the properties in the solution. 相似文献