The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Cristina Darrigo - One of the best experts on this subject based on the ideXlab platform.
-
a Critical Concentration of n terminal pyroglutamylated amyloid beta drives the misfolding of ab1 42 into more toxic aggregates
The International Journal of Biochemistry & Cell Biology, 2016Co-Authors: Denise Galante, Francesco Simone Ruggeri, Giovanni Dietler, Francesca Pellistri, Elena Gatta, Alessandro Corsaro, Tullio Florio, Angelo Perico, Cristina DarrigoAbstract:Abstract A wide consensus based on robust experimental evidence indicates pyroglutamylated amyloid-β isoform (AβpE3-42) as one of the most neurotoxic peptides involved in the onset of Alzheimer’s disease. Furthermore, AβpE3-42 co-oligomerized with excess of Aβ1-42, produces oligomers and aggregates that are structurally distinct and far more cytotoxic than those made from Aβ1-42 alone. Here, we investigate quantitatively the influence of AβpE3-42 on biophysical properties and biological activity of Aβ1-42. We tested different ratios of AβpE3-42/Aβ1-42 mixtures finding a correlation between the biological activity and the structural conformation and morphology of the analyzed mixtures. We find that a mixture containing 5% AβpE3-42, induces the highest disruption of intracellular calcium homeostasis and the highest neuronal toxicity. These data correlate to an high content of relaxed antiparallel β-sheet structure and the coexistence of a population of big spheroidal aggregates together with short fibrils. Our experiments provide also evidence that AβpE3-42 causes template-induced misfolding of Aβ1-42 at ratios below 33%. This means that there exists a Critical Concentration required to have seeding on Aβ1-42 aggregation, above this threshold, the seed effect is not possible anymore and AβpE3-42 controls the total aggregation kinetics.
Francesco Simone Ruggeri - One of the best experts on this subject based on the ideXlab platform.
-
a Critical Concentration of n terminal pyroglutamylated amyloid beta drives the misfolding of ab1 42 into more toxic aggregates
The International Journal of Biochemistry & Cell Biology, 2016Co-Authors: Denise Galante, Francesco Simone Ruggeri, Giovanni Dietler, Francesca Pellistri, Elena Gatta, Alessandro Corsaro, Tullio Florio, Angelo Perico, Cristina DarrigoAbstract:Abstract A wide consensus based on robust experimental evidence indicates pyroglutamylated amyloid-β isoform (AβpE3-42) as one of the most neurotoxic peptides involved in the onset of Alzheimer’s disease. Furthermore, AβpE3-42 co-oligomerized with excess of Aβ1-42, produces oligomers and aggregates that are structurally distinct and far more cytotoxic than those made from Aβ1-42 alone. Here, we investigate quantitatively the influence of AβpE3-42 on biophysical properties and biological activity of Aβ1-42. We tested different ratios of AβpE3-42/Aβ1-42 mixtures finding a correlation between the biological activity and the structural conformation and morphology of the analyzed mixtures. We find that a mixture containing 5% AβpE3-42, induces the highest disruption of intracellular calcium homeostasis and the highest neuronal toxicity. These data correlate to an high content of relaxed antiparallel β-sheet structure and the coexistence of a population of big spheroidal aggregates together with short fibrils. Our experiments provide also evidence that AβpE3-42 causes template-induced misfolding of Aβ1-42 at ratios below 33%. This means that there exists a Critical Concentration required to have seeding on Aβ1-42 aggregation, above this threshold, the seed effect is not possible anymore and AβpE3-42 controls the total aggregation kinetics.
Thomas B Schon - One of the best experts on this subject based on the ideXlab platform.
-
reevaluation of the Critical Concentration for drug susceptibility testing of mycobacterium tuberculosis against pyrazinamide using wild type mic distributions and pnca gene sequencing
Antimicrobial Agents and Chemotherapy, 2012Co-Authors: Jim Werngren, Erik Sturegard, P Jureen, Kristian Angeby, Sven Hoffner, Thomas B SchonAbstract:ABSTRACT Pyrazinamide (PZA) is a potent first-line agent for the treatment of tuberculosis (TB) with activity also against a significant part of drug-resistant Mycobacterium tuberculosis strains. Since PZA is active only at acid pH, testing for susceptibility to PZA is difficult and insufficiently reproducible. The recommended Critical Concentration for PZA susceptibility (MIC, 100 mg/liter) used in the Bactec systems (460 and MGIT 960) has not been Critically evaluated against wild-type MIC distributions in clinical isolates of Mycobacterium tuberculosis. Using the Bactec MGIT 960 system, we determined the PZA MICs for 46 clinical M. tuberculosis isolates and compared the results to pncA sequencing and previously obtained Bactec 460 data. For consecutive clinical isolates ( n = 15), the epidemiological wild-type cutoff (ECOFF) for PZA was 64 mg/liter (MIC distribution range, ≤8 to 64 mg/liter), and no pncA gene mutations were detected. In strains resistant in both Bactec systems ( n = 18), the PZA MICs ranged from 256 to ≥1,024 mg/liter. The discordances between pncA sequencing, susceptibility results in Bactec 460, and MIC determinations in Bactec MGIT 960 were mainly observed in strains with MICs close to or at the ECOFF. We conclude that in general, wild-type and resistant strains were clearly separated and correlated to pncA mutations, although some isolates with MICs close to the ECOFF cause reproducibility problems within and between methods. To solve this issue, we suggest that isolates with MICs of ≤64 mg/liter be classified susceptible, that an intermediary category be introduced at 128 mg/liter, and that strains with MICs of >128 mg/liter be classified resistant.
Xiangling Ji - One of the best experts on this subject based on the ideXlab platform.
-
Critical Concentration and scaling exponents of one soluble polyimide from dilute to semidilute entangled solutions
Polymer, 2016Co-Authors: Ensong Zhang, Zhixin Dong, Xiangling JiAbstract:Abstract A soluble polyimide (6FDA-TFDB) was synthesized and its properties in solution were investigated. The relationship between specific viscosity and Concentration is established using rheometer and applying Zimm model (dilute solution), Rouse–Zimm model (semidilute unentangled solution), and Doi–Edwards model (semidilute entangled solution). In addition, the overlapped Concentration (C*) and semidilute entangled Concentration (Ce) are determined. Results showed that all of the scaling exponents are higher than the theoretical values. The influence of factors, namely, electrostatic interaction, hydrogen bonding, dipole–dipole interaction and polydispersity index under different conditions (i.e., temperature, salt, and solvent) on Critical Concentration and scaling exponents are investigated extensively. In order to confirm the related conclusions, two soluble polyimides with different chemical structures are also synthesized and compared with the above results. The reasons for the deviation of scaling exponents are also discussed.
Denise Galante - One of the best experts on this subject based on the ideXlab platform.
-
a Critical Concentration of n terminal pyroglutamylated amyloid beta drives the misfolding of ab1 42 into more toxic aggregates
The International Journal of Biochemistry & Cell Biology, 2016Co-Authors: Denise Galante, Francesco Simone Ruggeri, Giovanni Dietler, Francesca Pellistri, Elena Gatta, Alessandro Corsaro, Tullio Florio, Angelo Perico, Cristina DarrigoAbstract:Abstract A wide consensus based on robust experimental evidence indicates pyroglutamylated amyloid-β isoform (AβpE3-42) as one of the most neurotoxic peptides involved in the onset of Alzheimer’s disease. Furthermore, AβpE3-42 co-oligomerized with excess of Aβ1-42, produces oligomers and aggregates that are structurally distinct and far more cytotoxic than those made from Aβ1-42 alone. Here, we investigate quantitatively the influence of AβpE3-42 on biophysical properties and biological activity of Aβ1-42. We tested different ratios of AβpE3-42/Aβ1-42 mixtures finding a correlation between the biological activity and the structural conformation and morphology of the analyzed mixtures. We find that a mixture containing 5% AβpE3-42, induces the highest disruption of intracellular calcium homeostasis and the highest neuronal toxicity. These data correlate to an high content of relaxed antiparallel β-sheet structure and the coexistence of a population of big spheroidal aggregates together with short fibrils. Our experiments provide also evidence that AβpE3-42 causes template-induced misfolding of Aβ1-42 at ratios below 33%. This means that there exists a Critical Concentration required to have seeding on Aβ1-42 aggregation, above this threshold, the seed effect is not possible anymore and AβpE3-42 controls the total aggregation kinetics.