| 1. |
- Alstermark, Bror, et al.
(författare)
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Building a realistic neuronal model that simulates multi-joint arm and hand movements in 3D space
- 2007
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Ingår i: HFSP Journal. - : Informa UK Limited. - 1955-2068. ; 1:4, s. 209-214
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Tidskriftsartikel (refereegranskat)abstract
- The question as to how the brain controls voluntary movements of the arm and hand still remains largely unsolved despite much research focused on behavioral studies, neurophysiological investigations, and neuronal modeling in computer science. This is because behavioral studies are usually performed without detailed knowledge of the underlying neuronal networks, neurophysiological studies often lack an understanding of the function, and neuronal models are frequently focused on a particular control problem with restricted knowledge of the underlying neuronal networks involved. Therefore, it seems appropriate to start by trying to integrate knowledge of neuronal networks with known function and computer based neuronal models to seek more realistic models that can better control robots or artificial limbs and hands. We propose to combine knowledge of a behavioral model for reaching with the hand toward an object, which is based on detailed knowledge of the underlying neuronal network, and a neuronal model that includes several functional levels, from the planning level via intermediate levels to the final level of control of motoneurons and muscles.
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| 2. |
- Bromley, Elizabeth H. C., et al.
(författare)
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The Tumbleweed: towards a synthetic protein motor
- 2009
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Ingår i: HFSP Journal. - : Informa UK Limited. - 1955-2068. ; 3:3, s. 204-212
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Tidskriftsartikel (refereegranskat)abstract
- Biomolecular motors have inspired the design and construction of artificial nanoscale motors and machines based on nucleic acids, small molecules, and inorganic nanostructures. However, the high degree of sophistication and efficiency of biomolecular motors, as well as their specific biological function, derives from the complexity afforded by protein building blocks. Here, we discuss a novel bottom-up approach to understanding biological motors by considering the construction of synthetic protein motors. Specifically, we present a design for a synthetic protein motor that moves along a linear track, dubbed the "Tumbleweed." This concept uses three discrete ligand-dependent DNA-binding domains to perform cyclically ligand-gated, rectified diffusion along a synthesized DNA molecule. Here we describe how de novo peptide design and molecular biology could be used to produce the Tumbleweed, and we explore the fundamental motor operation of such a design using numerical simulations. The construction of this and more sophisticated protein motors is an exciting challenge that is likely to enhance our understanding of the structure-function relationship in biological motors. [DOI: 10.2976/1.3111282]
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| 3. |
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| 4. |
- Falsig, Jeppe, et al.
(författare)
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Chemical and biophysical insights into the propagation of prion strains
- 2008
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Ingår i: HFSP JOURNAL. - : Informa UK Limited. - 1955-2068. ; 2:6, s. 332-341
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Tidskriftsartikel (refereegranskat)abstract
- Transmissible spongiform encephalopathies (TSEs) are lethal infectious neurodegenerative diseases. TSEs are caused by prions, infectious agents lacking informational nucleic acids, and possibly identical with higher-order aggregates of the cellular glycolipoprotein PrPC. Prion strains are derived from TSE isolates that, even after inoculation into genetically identical hosts, cause disease with distinct patterns of protein aggregate deposition, incubation times, morphology of the characteristic brain damage, and cellular tropism. Most of these traits are relatively stable across serial passages. Here we review current techniques for studying prion strain differences in vivo and in cells, and discuss the strain phenomena in the general context of the knowledge gained from modeling prion fibril growth in vitro and in simple organisms.
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| 5. |
- Nordlund, Anna, et al.
(författare)
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SOD1-associated ALS : a promising system for elucidating the origin of protein-misfolding disease
- 2008
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Ingår i: HFSP Journal. - : Informa UK Limited. - 1955-2068. ; 2:6, s. 354-364
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Tidskriftsartikel (refereegranskat)abstract
- Amyotropic lateral sclerosis (ALS) is a neurodegenerative disease linked to misfolding and aggregation of the homodimeric enzyme superoxide dismutase (SOD1). In contrast to the precursors of other neurodegenerative diseases, SOD1 is a soluble and simple-to-study protein with immunoglobulin-like structure. Also, there are more than 120 ALS-provoking SOD1 mutations at the disposal for detailed elucidation of the disease-triggering factors at molecular level. In this article, we review recent progress in the characterization of the folding and assembly pathway of the SOD1 dimer and how this is affected by ALS-provoking mutations. Despite the diverse nature of these mutations, the results offer so far a surprising simplicity. The ALS-provoking mutations decrease either protein stability or net repulsive charge: the classical hallmarks for a disease mechanism triggered by association of non-native protein. In addition, the mutant data identifies immature SOD1 monomers as the species from which the cytotoxic pathway emerges, and point at compromised folding cooperativity as a key disease determinant. The relative ease by which these data can be obtained makes SOD1 a promising model for elucidating also the origin of other neurodegenerative diseases where the precursor proteins are structurally more elusive.
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| 6. |
- Thill, Serge, et al.
(författare)
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Understanding complex behaviors by analyzing optimized models: C. elegans gradient navigation
- 2007
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Ingår i: HFSP Journal. - : Taylor & Francis. - 1955-2068. ; 1:4, s. 263-273
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Tidskriftsartikel (refereegranskat)abstract
- We study how individual components of a complex behavior, so‐called behavioral units, should be sequentially arranged when the overall goal is energy efficiency. We apply an optimization scheme to an existing probabilistic model of C. elegans chemical gradient navigation and find a family of solutions that share common properties. This family is used to analyze general principles of behavioral unit organization, which give rise to search strategies that match qualitatively with those observed in the animal. Specifically, the reorientation behavior emerging in energy efficient virtual worm searchers mimics the pirouette strategy observed in C. elegans, and the virtual worms dwell at the peak of the gradient. Our model predicts that pirouettes are in part associated with the inability to evaluate the gradient during a turn and that the animal does not act upon gradient information while reversing. Together, our results indicate that energy efficiency is an important factor in determining C. elegans gradient navigation. Our framework for the analysis of complex behaviors may, in the future, be used as part of an integrated approach to studying the neural basis of these behaviors.
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