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991.
Thijs W.G. van der Heijden Daniel J. Read Oliver G. Harlen Paul van der Schoot Sarah A. Harris Cornelis Storm 《Biophysical journal》2020,119(11):2240
Assessing the structural properties of large proteins is important to gain an understanding of their function in, e.g., biological systems or biomedical applications. We propose a method to examine the mechanical properties of proteins subject to applied forces by means of multiscale simulation. Both stretching and torsional forces are considered, and these may be applied independently of each other. As a proof of principle, we apply torsional forces to a coarse-grained continuum model of the antibody protein immunoglobulin G using fluctuating finite element analysis and use it to identify the area of strongest deformation. This region is essential to the torsional properties of the molecule as a whole because it represents the softest, most deformable domain. Zooming in, this part of the molecule is subjected to torques and stretching forces using molecular dynamics simulations on an atomistically resolved level to investigate its torsional properties. We calculate the torsional resistance as a function of the rotation of the domain while subjecting it to various stretching forces. From this, we assess how the measured twist-torque profiles develop with increasing stretching force and show that they exhibit torsion stiffening, in qualitative agreement with experimental findings. We argue that combining the twist-torque profiles for various stretching forces effectively results in a combined force-torque spectroscopy analysis, which may serve as a mechanical signature for a biological macromolecule. 相似文献
992.
Marcus Weinguny Peter Eisenhut Gerald Klanert Nikolaus Virgolini Nicolas Marx Andreas Jonsson Daniel Ivansson Ann Lövgren Nicole Borth 《Biotechnology and bioengineering》2020,117(11):3435-3447
Chinese hamster ovary (CHO) cells produce a large share of today's biopharmaceuticals. Still, the generation of satisfactory producer cell lines is a tedious undertaking. Recently, it was found that CHO cells, when exposed to new environmental conditions, modify their epigenome, suggesting that cells adapt their gene expression pattern to handle new challenges. The major aim of the present study was to employ artificially induced, random changes in the DNA-methylation pattern of CHO cells to diversify cell populations and consequently increase the finding of cell lines with improved cellular characteristics. To achieve this, DNA methyltransferases and/or the ten-eleven translocation enzymes were downregulated by RNA interference over a time span of ∼16 days. Methylation analysis of the resulting cell pools revealed that the knockdown of DNA methyltransferases was highly effective in randomly demethylating the genome. The same approach, when applied to stable CHO producer cells resulted in (a) an increased productivity diversity in the cell population, and (b) a higher number of outliers within the population, which resulted in higher specific productivity and titer in the sorted cells. These findings suggest that epigenetics play a previously underestimated, but actually important role in defining the overall cellular behavior of production clones. 相似文献
993.
Meghan F. Maciejewski Cynthia Jiang Yoel E. Stuart Daniel I. Bolnick 《Evolution; international journal of organic evolution》2020,74(4):749-763
Since the New Synthesis, most migration-selection balance theory has predicted that there should be negligible differentiation over small spatial scales (relative to dispersal), because gene flow should erode any effect of divergent selection. Nevertheless, there are classic examples of microgeographic divergence, which theory suggests can arise under specific conditions: exceptionally strong selection, phenotypic plasticity in philopatric individuals, or nonrandom dispersal. Here, we present evidence of microgeographic morphological variation within lake and stream populations of threespine stickleback (Gasterosteus aculeatus). It seems reasonable to assume that a given lake or stream population of fish is well-mixed. However, we found this assumption to be untenable. We examined trap-to-trap variation in 34 morphological traits measured on stickleback from 16 lakes and 16 streams. Most traits varied appreciably among traps within populations. Both between-trap distance and microhabitat characteristics such as depth and substrate explained some of the within-population morphological variance. Microhabitat was also associated with genotype at particular loci but there was no genetic isolation by distance, implying that heritable habitat preferences may contribute to microgeographic variation. Our study adds to growing evidence that microgeographic divergence can occur across small spatial scales within individuals’ daily dispersal neighborhood where gene flow is expected to be strong. 相似文献
994.
Anjos Marcia S. Bitencourt Jamille A. Nunes Lorena A. Sarmento-Soares Luisa M. Carvalho Daniel C. Armbruster Jonathan W. Affonso Paulo R. A. M. 《Hydrobiologia》2020,847(2):563-578
Hydrobiologia - Integrative approaches are particularly useful to resolve taxonomic uncertainties in species-rich groups that have undergone explosive radiation, such as Hypostomini (suckermouth... 相似文献
995.
996.
Meir Schechter Merav Atias Suaad Abd Elhadi Dana Davidi Daniel Gitler Ronit Sharon 《The Journal of biological chemistry》2020,295(52):18076
α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson''s disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we investigate the associations of α-Syn with the acidic phosphoinositides (PIPs), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). Our results show that α-Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor protein 2 (AP2) at clathrin-coated pits. Using endocytosis of transferrin as an indicator for clathrin-mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI(4,5)P2 levels on the plasma membrane. In accord with their effects on PI(4,5)P2 levels, the PD associated A30P, E46K, and A53T mutations in α-Syn further enhance CME in neuronal and nonneuronal cells. However, lysine to glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, which interfere with phospholipid binding, are ineffective in enhancing CME. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by the α-Syn mutations and associates with their effects on PI(4,5)P2 levels, however, with the exception of the A30P mutation. This study provides evidence for a critical involvement of PIPs in α-Syn–mediated membrane trafficking. 相似文献
997.
998.
Javier Hernán Rojo Daniel Alfredo Fernández Daniel Enrique Figueroa Claudia Clementina Boy 《Journal of fish biology》2020,96(4):956-967
This study reports the phenotypic and genetic differences between individuals of puyen Galaxias maculatus from two sites in the same river basin in Tierra del Fuego National Park, southern South America. Individuals from the two sampling sites presented morphometric and genetic differences. The morphometric differences indicated that individuals from Laguna Negra (LN) were short and more robust and had large eyes, whereas those from Arroyo Negro (AN) were thin and elongated and had small eyes. Genetic differences showed that AN individuals had a greater genetic structuration and an older demographic history than LN individuals. The results of this study affirmed that the individuals from the two sampling sites belong to different populations with a high degree of isolation. The demographic history could indicate that the individuals of G. maculatus which migrated to northern areas during the last glaciation settled in the Beagle Channel after its formation. The LN population could have originated after the retreat of the glaciers, migrating from AN. 相似文献
999.
Cyrille Gavazzi Catherine Isel Emilie Fournier Vincent Moules Annie Cavalier Daniel Thomas Bruno Lina Roland Marquet 《Nucleic acids research》2013,41(2):1241-1254
The genome of influenza A viruses (IAV) is split into eight viral RNAs (vRNAs) that are encapsidated as viral ribonucleoproteins. The existence of a segment-specific packaging mechanism is well established, but the molecular basis of this mechanism remains to be deciphered. Selective packaging could be mediated by direct interaction between the vRNA packaging regions, but such interactions have never been demonstrated in virions. Recently, we showed that the eight vRNAs of a human H3N2 IAV form a single interaction network in vitro that involves regions of the vRNAs known to contain packaging signals in the case of H1N1 IAV strains. Here, we show that the eight vRNAs of an avian H5N2 IAV also form a single network of interactions in vitro, but, interestingly, the interactions and the regions of the vRNAs they involve differ from those described for the human H3N2 virus. We identified the vRNA sequences involved in five of these interactions at the nucleotide level, and in two cases, we validated the existence of the interaction using compensatory mutations in the interacting sequences. Electron tomography also revealed significant differences in the interactions taking place between viral ribonucleoproteins in H5N2 and H3N2 virions, despite their canonical ‘7 + 1’ arrangement. 相似文献
1000.