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  • 1
    Online Resource
    Online Resource
    How old are dense-core vesicles residing in en passant boutons: simulation of the mean age of dense-core vesicles in axonal arbours accounting for resident and transiting vesicle populations
    The Royal Society ; 2020
    In:  Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences Vol. 476, No. 2241 ( 2020-09)
    Details
    In: Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, The Royal Society, Vol. 476, No. 2241 ( 2020-09)
    Abstract: In neurons, neuropeptides are synthesized in the soma and are then transported along the axon in dense-core vesicles (DCVs). DCVs are captured in varicosities located along the axon terminal called en passant boutons, which are active terminal sites that accumulate and release neurotransmitters. Recently developed experimental techniques allow for the estimation of the age of DCVs in various locations in the axon terminal. Accurate simulation of the mean age of DCVs in boutons requires the development of a model that would account for resident, transiting-anterograde and transiting-retrograde DCV populations. In this paper, such a model is developed. The model is applied to simulating DCV transport in Drosophila type II motoneurons. The model simulates DCV transport and capture in the axon terminals and makes it possible to predict the age density distribution of DCVs in en passant boutons as well as DCV mean age in boutons. The predicted prevalence of older organelles in distal boutons may explain the ‘dying back’ pattern of axonal degeneration observed in dopaminergic neurons in Parkinson's disease. The predicted difference of two hours between the age of older DCVs residing in distal boutons and the age of younger DCVs residing in proximal boutons is consistent with an approximate estimate of age difference deduced from experimental observations. The age density of resident DCVs is found to be bimodal, which is because DCVs are captured from two transiting states: the anterograde transiting state that contains younger DCVs and the retrograde transiting state that contains older DCVs.
    Type of Medium: Online Resource
    ISSN: 1364-5021 , 1471-2946
    URL: Article
    DOI: 10.1098/rspa.2020.0454
    Language: English
    Publisher: The Royal Society
    Publication Date: 2020
    detail.hit.zdb_id: 209241-4
    detail.hit.zdb_id: 1460987-3
    SSG: 11
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  • 2
    Online Resource
    Online Resource
    Computational investigation of the effect of reduced dynein velocity and reduced cargo diffusivity on slow axonal transport
    The Royal Society ; 2023
    In:  Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences Vol. 479, No. 2271 ( 2023-03)
    Details
    In: Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, The Royal Society, Vol. 479, No. 2271 ( 2023-03)
    Abstract: Contributions of three components of slow axonal transport (SAT) were studied using a computational model: the anterograde motor (kinesin)-driven component, the retrograde motor (dynein)-driven component and the diffusion-driven component. The contribution of these three components of SAT was investigated in three different segments of the axon: the proximal portion, the central portion, and the distal portion of the axon. MAP1B protein was used as a model system to study SAT because there are published experimental data reporting MAP1B distribution along the axon length and average velocity of MAP1B transport in the axon. This allows the optimization approach to be used to find values of model kinetic constants that give the best fit with published experimental data. The effects of decreasing the value of cargo diffusivity on the diffusion-driven component of SAT and decreasing the value of dynein velocity on the retrograde motor-driven component of SAT were investigated. We found that for the case when protein diffusivity and dynein velocity are very small, it is possible to obtain an analytical solution to model equations. We found that, in this case, the protein concentration in the axon is uniform. This shows that anterograde motor-driven transport alone cannot simulate a variation of cargo concentration in the axon. Most proteins are non-uniformly distributed in axons. They may exhibit, for example, an increased concentration closer to the synapse. The need to reproduce a non-uniform distribution of protein concentration may explain why SAT is bidirectional (in addition to an anterograde component, it also contains a retrograde component).
    Type of Medium: Online Resource
    ISSN: 1364-5021 , 1471-2946
    URL: Article
    DOI: 10.1098/rspa.2022.0672
    Language: English
    Publisher: The Royal Society
    Publication Date: 2023
    detail.hit.zdb_id: 209241-4
    detail.hit.zdb_id: 1460987-3
    SSG: 11
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  • 3
    Online Resource
    Online Resource
    Party Control of Historians in the Novosibirsk Academgorodok (1970)
    Novosibirsk State University (NSU) ; 2021
    In:  Vestnik NSU. Series: History and Philology Vol. 20, No. 1 ( 2021), p. 136-148
    Details
    In: Vestnik NSU. Series: History and Philology, Novosibirsk State University (NSU), Vol. 20, No. 1 ( 2021), p. 136-148
    Abstract: The resolution by the bureau of the Novosibirsk regional committee of the CPSU “On the work of the Institute of History, Philology and Philosophy of the Siberian Branch of the Academy of Sciences of the USSR” dated May 26, 1970 reflects a system intended to control over the activities of academic society, primarily humanitarians. The party considered the scholars, and the historians in particular, as a “fighter” in the ideological battle who had to adhere to the principle of “Marxism-Leninism”, and, in fact, to all official guidelines consistently developed by the CPSU. The focus of this document is scholars who were involved in research projects of political nature. The resolution contains harsh assessments towards a number of “mistake” in the scientific activities of this institution. Among these mistakes the authors of the document mention the lack of adherence to ideological principles, widely spread in the collective of scholars of the Institute of history. Historians from the Institute get a lot of criticism from the CPSU functionaries for the absence of political and organizational public work in the city, and also for week methodological and ideological influence on the other scientific organizations in Academgorodok, as well as on the departments and sections of social sciences in the Novosibirsk universities. On the whole, this reflected a general conservative trend in accordance with the requirements of the CPSU of the 1960–1970s.
    Type of Medium: Online Resource
    ISSN: 1818-7919
    Uniform Title: Партийный контроль за деятельностью историков в новосибирском Академгородке (1970 год)
    URL: Issue
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.25205/1818-7919-2021-20
    DOI: 10.25205/1818-7919-2021-20-1
    DOI: 10.25205/1818-7919
    DOI: 10.25205/1818-7919-2021-20-1-136-148
    Language: Russian
    Publisher: Novosibirsk State University (NSU)
    Publication Date: 2021
    SSG: 7,39
    SSG: 7,41
    SSG: 7,11
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  • 4
    Online Resource
    Online Resource
    Differences in spatial versus temporal reaction norms for spring and autumn phenological events
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 49 ( 2020-12-08), p. 31249-31258
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 49 ( 2020-12-08), p. 31249-31258
    Abstract: For species to stay temporally tuned to their environment, they use cues such as the accumulation of degree-days. The relationships between the timing of a phenological event in a population and its environmental cue can be described by a population-level reaction norm. Variation in reaction norms along environmental gradients may either intensify the environmental effects on timing (cogradient variation) or attenuate the effects (countergradient variation). To resolve spatial and seasonal variation in species’ response, we use a unique dataset of 91 taxa and 178 phenological events observed across a network of 472 monitoring sites, spread across the nations of the former Soviet Union. We show that compared to local rates of advancement of phenological events with the advancement of temperature-related cues (i.e., variation within site over years), spatial variation in reaction norms tend to accentuate responses in spring (cogradient variation) and attenuate them in autumn (countergradient variation). As a result, among-population variation in the timing of events is greater in spring and less in autumn than if all populations followed the same reaction norm regardless of location. Despite such signs of local adaptation, overall phenotypic plasticity was not sufficient for phenological events to keep exact pace with their cues—the earlier the year, the more did the timing of the phenological event lag behind the timing of the cue. Overall, these patterns suggest that differences in the spatial versus temporal reaction norms will affect species’ response to climate change in opposite ways in spring and autumn.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2002713117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Reactibodies generated by kinetic selection couple chemical reactivity with favorable protein dynamics
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 38 ( 2011-09-20), p. 15954-15959
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 38 ( 2011-09-20), p. 15954-15959
    Abstract: Igs offer a versatile template for combinatorial and rational design approaches to the de novo creation of catalytically active proteins. We have used a covalent capture selection strategy to identify biocatalysts from within a human semisynthetic antibody variable fragment library that uses a nucleophilic mechanism. Specific phosphonylation at a single tyrosine within the variable light-chain framework was confirmed in a recombinant IgG construct. High-resolution crystallographic structures of unmodified and phosphonylated Fabs display a 15-Å-deep two-chamber cavity at the interface of variable light ( V L ) and variable heavy ( V H ) fragments having a nucleophilic tyrosine at the base of the site. The depth and structure of the pocket are atypical of antibodies in general but can be compared qualitatively with the catalytic site of cholinesterases. A structurally disordered heavy chain complementary determining region 3 loop, constituting a wall of the cleft, is stabilized after covalent modification by hydrogen bonding to the phosphonate tropinol moiety. These features and presteady state kinetics analysis indicate that an induced fit mechanism operates in this reaction. Mutations of residues located in this stabilized loop do not interfere with direct contacts to the organophosphate ligand but can interrogate second shell interactions, because the H3 loop has a conformation adjusted for binding. Kinetic and thermodynamic parameters along with computational docking support the active site model, including plasticity and simple catalytic components. Although relatively uncomplicated, this catalytic machinery displays both stereo- and chemical selectivity. The organophosphate pesticide paraoxon is hydrolyzed by covalent catalysis with rate-limiting dephosphorylation. This reactibody is, therefore, a kinetically selected protein template that has enzyme-like catalytic attributes.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1108460108
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Protein sequence design by conformational landscape optimization
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 11 ( 2021-03-16)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 11 ( 2021-03-16)
    Abstract: The protein design problem is to identify an amino acid sequence that folds to a desired structure. Given Anfinsen’s thermodynamic hypothesis of folding, this can be recast as finding an amino acid sequence for which the desired structure is the lowest energy state. As this calculation involves not only all possible amino acid sequences but also, all possible structures, most current approaches focus instead on the more tractable problem of finding the lowest-energy amino acid sequence for the desired structure, often checking by protein structure prediction in a second step that the desired structure is indeed the lowest-energy conformation for the designed sequence, and typically discarding a large fraction of designed sequences for which this is not the case. Here, we show that by backpropagating gradients through the transform-restrained Rosetta (trRosetta) structure prediction network from the desired structure to the input amino acid sequence, we can directly optimize over all possible amino acid sequences and all possible structures in a single calculation. We find that trRosetta calculations, which consider the full conformational landscape, can be more effective than Rosetta single-point energy estimations in predicting folding and stability of de novo designed proteins. We compare sequence design by conformational landscape optimization with the standard energy-based sequence design methodology in Rosetta and show that the former can result in energy landscapes with fewer alternative energy minima. We show further that more funneled energy landscapes can be designed by combining the strengths of the two approaches: the low-resolution trRosetta model serves to disfavor alternative states, and the high-resolution Rosetta model serves to create a deep energy minimum at the design target structure.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2017228118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Impact of chaotic dynamics on the performance of metaheuristic optimization algorithms: An experimental analysis
    Elsevier BV ; 2022
    In:  Information Sciences Vol. 587 ( 2022-03), p. 692-719
    Details
    In: Information Sciences, Elsevier BV, Vol. 587 ( 2022-03), p. 692-719
    Type of Medium: Online Resource
    ISSN: 0020-0255
    URL: Article
    DOI: 10.1016/j.ins.2021.10.076
    RVK:
    SA 5420
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 218760-7
    detail.hit.zdb_id: 1478990-5
    SSG: 24,1
    SSG: 7,11
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  • 8
    Online Resource
    Online Resource
    Chaplygin sleigh with periodically oscillating internal mass
    IOP Publishing ; 2017
    In:  EPL (Europhysics Letters) Vol. 119, No. 6 ( 2017-09-01), p. 60008-
    Details
    In: EPL (Europhysics Letters), IOP Publishing, Vol. 119, No. 6 ( 2017-09-01), p. 60008-
    Type of Medium: Online Resource
    ISSN: 0295-5075 , 1286-4854
    URL: Article
    DOI: 10.1209/0295-5075/119/60008
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2017
    detail.hit.zdb_id: 1465366-7
    detail.hit.zdb_id: 165776-8
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