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- D'Accolti, D., et al.
(författare)
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Online Classification of Transient EMG Patterns for the Control of the Wrist and Hand in a Transradial Prosthesis
- 2023
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Ingår i: IEEE Robotics and Automation Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 2377-3766 .- 2377-3774. ; 8:2, s. 1045-1052
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Tidskriftsartikel (refereegranskat)abstract
- Decoding human motor intentions by processing electrophysiological signals is a crucial, yet unsolved, challenge for the development of effective upper limb prostheses. Pattern recognition of continuous myoelectric (EMG) signals represents the state-of-art for multi-DoF prosthesis control. However, this approach relies on the unreliable assumption that repeatable muscular contractions produce repeatable patterns of steady-state EMGs. Here, we propose an approach for decoding wrist and hand movements by processing the signals associated with the onset of contraction (transient EMG). Specifically, we extend the concept of a transient EMG controller for the control of both wrist and hand, and tested it online. We assessed it with one transradial amputee and 15 non-amputees via the Target Achievement Control test. Non-amputees successfully completed 95% of the trials with a median completion time of 17 seconds, showing a significant learning trend (p < 0.001). The transradial amputee completed about the 80% of the trials with a median completion time of 26 seconds. Although the performance proved comparable with earlier studies, the long completion times suggest that the current controller is not yet clinically viable. However, taken collectively, our outcomes reinforce earlier hypothesis that the transient EMG could represent a viable alternative to steady-state pattern recognition approaches.
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| 3. |
- Habchi, Johnny, et al.
(författare)
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Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 114:2, s. 200-208
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a readout the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.
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| 4. |
- Limbocker, Ryan, et al.
(författare)
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Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-β peptide (Aβ42) are key pathogenic agents in Alzheimer’s disease (AD). To investigate the relationship between Aβ42 aggregation and its cytotoxicity and the influence of a potential drug on both phenomena, we have studied the effects of trodusquemine. This aminosterol enhances the rate of aggregation by promoting monomer-dependent secondary nucleation, but significantly reduces the toxicity of the resulting oligomers to neuroblastoma cells by inhibiting their binding to the cellular membranes. When administered to a C. elegans model of AD, we again observe an increase in aggregate formation alongside the suppression of Aβ42-induced toxicity. In addition to oligomer displacement, the reduced toxicity could also point towards an increased rate of conversion of oligomers to less toxic fibrils. The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD.
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| 5. |
- Rodriguez Camargo, Diana C., et al.
(författare)
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Surface-Catalyzed Secondary Nucleation Dominates the Generation of Toxic IAPP Aggregates
- 2021
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of the human islet amyloid polypeptide (IAPP) is associated with diabetes type II. A quantitative understanding of this connection at the molecular level requires that the aggregation mechanism of IAPP is resolved in terms of the underlying microscopic steps. Here we have systematically studied recombinant IAPP, with amidated C-terminus in oxidised form with a disulphide bond between residues 3 and 7, using thioflavin T fluorescence to monitor the formation of amyloid fibrils as a function of time and IAPP concentration. We used global kinetic analyses to connect the macroscopic measurements of aggregation to the microscopic mechanisms, and show that the generation of new aggregates is dominated by the secondary nucleation of monomers on the fibril surface. We then exposed insulinoma cells to aliquots extracted from different time points of the aggregation process, finding the highest toxicity at the midpoint of the reaction, when the secondary nucleation rate reaches its maximum. These results identify IAPP oligomers as the most cytotoxic species generated during IAPP aggregation, and suggest that compounds that target secondary nucleation of IAPP could be most effective as therapeutic candidates for diabetes type II.
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