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941.
Sergey A. Samsonov Emilia A. Lubecka Krzysztof K. Bojarski Robert Ganzynkowicz Adam Liwo 《Biopolymers》2019,110(8):e23269
Heparin belongs to glycosaminoglycans (GAGs), a class of periodic linear anionic polysaccharides, which are functionally important components of the extracellular matrix owing to their interactions with various protein targets. Heparin is known to be involved in many cell signaling processes, while the experimental data available for heparin are significantly more abundant than for other GAGs. At the same time, the length and conformational flexibility of the heparin represent major challenges for its theoretical analysis. Coarse-grained (CG) approaches, which enable us to extend the size- and time-scale by orders of magnitude owing to reduction of system representation, appear, therefore, to be useful in simulating these systems. In this work, by using umbrella-sampling molecular dynamics simulations, we derived and parameterized the CG backbone-local potentials of heparin chains and the orientational potentials for the interactions of heparin with amino acid side chains to be further included in the physics-based Unified Coarse-Grained Model of biological macromolecules. With these potentials, simulations of extracellular matrix processes where both heparin and multiple proteins participate will be possible. 相似文献
942.
Leander A. H. Petersen Christian Lieven Subir K. Nandy John Villadsen Sten B. Jørgensen Ib Christensen Krist V. Gernaey 《Biotechnology and bioengineering》2019,116(11):2884-2895
The methanotrophic bacterium Methylococcus capsulatus is capable of assimilating methane and oxygen into protein-rich biomass, however, the diverse metabolism of the microorganism also allows for several undesired cometabolic side-reactions to occur. In this study, the ammonia cometabolism in Methylococcus capsulatus is investigated using pulse experiments. Surprisingly Methylococcus capsulatus oxidizes ammonia to nitrate through a yet unknown mechanism and fixes molecular nitrogen even at a high dissolved oxygen tension. The observed phenomena can be modeled using 14 ordinary differential equations and 18 kinetic parameters, of which 6 were revealed by Morris screening to be identifiable from the experimental data. Monte Carlo simulations showed that the model was robust and accurate even with uncertainty in the parameter values as confirmed by statistical error analysis. 相似文献
943.
Ruobi Hu Hui Li Zhen Lei Qing Han Xiuyan Yu Na Zhou Xuehui Zhang Yiqing Mao Xi Wang David M. Irwin Gang Niu Huanran Tan 《Biotechnology and bioengineering》2019,116(10):2652-2661
A pyrogen test is crucial for evaluating the safety of drugs and medical equipment, especially those involved in injections. As existing pyrogen tests, including the rabbit pyrogen test, the limulus amoebocyte lysate (LAL) test and the monocyte activation test have limitations, development of new models for pyrogen testing is necessary. Here we develop a sensitive cell model for pyrogen test based on the lipopolysaccharides (LPS) signal pathway. TLR4, MD2, and CD14 play key roles in the LPS-mediated pyrogen reaction. We established a new TLR4/MD2/CD14-specific overexpressing knock-in cell model using the CRISPR/CAS9 technology and homologous recombination to detect LPS. Stimulation of our TLR4/CD14/MD2 knock-in cell line model with LPS leads to the release of the cytokines IL-6 and TNF-alpha, with a detection limit of 0.005 EU/ml, which is greatly lower than the lower limit of 0.015 EU/ml detected by the Tachypleus amebocyte lysate (TAL) assay. 相似文献
944.
FNU Namila Da Zhang Steven Traylor Tung Nguyen Nripen Singh Ranil Wickramasinghe Xianghong Qian 《Biotechnology and bioengineering》2019,116(10):2621-2631
A combined pore blockage and cake filtration model was applied to the virus filtration of an Fc-fusion protein using the three commercially available filters, F-1, F-2, and F-3 in a range of buffer conditions including sodium-phosphate and tris-acetate buffers with and without 200 mM NaCl at pH 7.5. The fouling behaviors of the three filters for the feed solutions spiked with minute virus of mice were described well by this combined model for all the solution conditions. This suggests that fouling of the virus filters is dominated by the pore blockage mechanism during the initial stage of the filtration and transformed to the cake filtration mechanism during the later stage of the filtration. Both flux and transmembrane resistance can be described well by this model. The pore blockage rate and the rate of increase of protein layer resistance over blocked pores are found to be affected by membrane properties as well as the solution conditions resulting from the modulation of interactions between virus, protein, and membrane by the solution conditions. 相似文献
945.
Kasra Tajdaran Katelyn Chan Jennifer Zhang Tessa Gordon Gregory H. Borschel 《Biotechnology and bioengineering》2019,116(2):405-414
Local administration of FK506, an FDA approved immunosuppressant with neuroregenerative properties, is a promising technique to achieve improved peripheral nerve regeneration while preventing the side effects associated with the systemic administration of this drug. Although considerable research has been devoted to the development of clinically suitable systems for local delivery of FK506 to the site of nerve injury and repair, the optimal dose of FK506 for enhancement of axon regeneration in the peripheral nerve has not yet been established. To this end, we devised a three-dimensional (3D) organotypic assay capable of mimicking the peripheral nerve. This assay consisted of a neonatal rat dorsal root ganglion (DRG) extending its neurites into the native peripheral nerve scaffold provided by an acellular nerve allograft (ANA). A novel 3D compartmented cell culture system was adapted from the 3D organotypic assay to achieve local delivery of FK506 just to the growing neurites in vitro and establish the required local dose of FK506 for peripheral nerve regeneration. A bimodal dose response was observed by culturing the entire DRG–ANA construct with media containing different concentrations of FK506. Low drug concentration of 1 pg/ml and high drug concentration of 100 ng/ml lead to the longest neurite extension in vitro. Furthermore, regardless of the FK506 concentration, concentrating the drug to the growing neurites resulted in significant increase in both neurite extension and neurite density, an effect that was not observed with the FK506 delivery to both neurites and neural cell bodies within DRG. The findings in this study provide valuable insight into the optimal local dose of FK506 for peripheral nerve regeneration. Furthermore, for the first time, this study suggests the potential interaction of FK506 with axons at the level of the growth cone. 相似文献
946.
Romina Lasry Testa Claudio Delpino Vanina Estrada Soledad M. Diaz 《Biotechnology and bioengineering》2019,116(8):2061-2073
Cyanobacteria have been considered as promising candidates for sustainable bioproduction from inexpensive raw materials, as they grow on light, carbon dioxide, and minimal inorganic nutrients. In this study, we present a genome-scale metabolic network model for Synechocystis sp. PCC 6803 and study the optimal design of the strain for ethanol production by using a mixed integer linear problem reformulation of a bilevel programming problem that identifies gene knockouts which lead to coupling between growth and product synthesis. Five mutants were found, where the in silico model predicts coupling between biomass growth and ethanol production in photoautotrophic conditions. The best mutant gives an in silico ethanol production of 1.054 mmol·gDW −1·h −1. 相似文献
947.
948.
Yang Cheng Baobing Yin Tianlu Hou Tianyang Chen Jian Ping 《Journal of cellular physiology》2019,234(9):16215-16225
This study aimed to validate the methylation of key genes in hepatocellular carcinoma (HCC) screened by bioinformatics analysis and explore whether they affected HCC cell proliferation, migration, and invasion. Using The Cancer Genome Atlas (TCGA) database, HCC-related differentially methylated positions (DMPs) were screened, genes corresponding to DMPs were selected, and prognosis-related genes were identified. A representative DMP was used to divide the DMPs into hyper- and hypomethylated groups. Expression of key genes in cell lines was detected using quantitative real-time polymerase chain reaction and western blot analysis. After treatment of HepG2 cells with 5-Aza-2′-deoxycytidine (5-Aza-DC), gene expression was observed. Bisulfite sequencing PCR assay was used to detect methylation frequency. Overexpressed GRASP lentiviral vectors were constructed to analyze their influence on cell proliferation, migration, and invasion using cell counting kit-8 and transwell assays. Forty-three HCC prognosis-related genes were screened using the TCGA database. cg00249511 (SCT) was used to divide the DMPs into hyper- and hypomethylated groups, distinguishing between high- and low-risk samples. The prognosis survival model constructed using 12 genes revealed the prognosis type. GRASP messenger RNA was downregulated in HepG2 and upregulated after 5-Aza-DC treatment. In HCC tissues, methylation frequency of GRASP was upregulated. GRASP overexpression inhibited HepG2 cell proliferation, invasion, and G-CSFR expression. Thus, GRASP might be a prognosis-related gene controlled by methylation. 相似文献
949.
Ching-Tsun Chang Wei-Chuan Chiang Yun-Chen Chang Michael K. Musyl Chi-Lu Sun Daniel J. Madigan Aaron B. Carlisle Hung-Hung Hsu Qi-Xuan Chang Nan-Jay Su Yuan-Shing Ho Chen-Te Tseng 《Journal of fish biology》2019,94(6):958-965
To gain a better understanding of the trophic ecology of Pacific blue marlin Makaira nigricans off eastern Taiwan, nitrogen and carbon stable isotopes (δ15N and δ13C) and Bayesian mixing models were used to explore trophic dynamics and potential ontogenetic feeding shifts across M. nigricans of different size classes. Makaira nigricans samples from east of Taiwan (n = 213) and Palau (n = 37), as well as their prey (n = 70), were collected during 2012 and 2013. Results indicated increases in δ15N with size, with values of larger size classes (> 200 cm eye-to-fork length; LEF) significantly higher than those < 200 cm LEF. Values of δ13C were negatively correlated with size. Makaira nigricans > 200 cm LEF had the highest estimated trophic position (4.44) and also exhibited ontogenetic changes in trophic position. Large M. nigricans fed more on dolphinfish Coryphaena hippurus and hairtail Trichiurus lepturus, while smaller M. nigricans consumed smaller forage fish (e.g., moonfish Mene maculata) and cephalopods. These changes may relate to greater swimming speeds and vertical habitat use in larger M. nigricans, allowing capture and consumption of larger prey items at higher trophic positions. The high trophic level of M. nigricans east of Taiwan confirms its important role as an apex predator in marine food webs and how ecological role changes with size. 相似文献
950.
Despite the prevalence of context‐dependent interaction transitions in ecological systems, their impacts on persistence and interaction diversity have scarcely been explored in complex ecological networks. By using multispecies bi‐directional and unidirectional consumer–resource models, representing a continuum of interaction transitions (sign change of interaction outcomes), we investigated the effects of structural interaction transitions on persistence (the fraction of remaining species) and long‐term interaction outcomes in random ecological networks. We found that high interaction strength of exploiting resources generally decreased persistence, and high strength of providing resources increased persistence when the strength of exploiting resources was low in more complex networks; also, the networks with high persistence had a high proportion of mutualistic interactions relative to antagonistic interactions present initially and over the long term. The shifting of interaction strengths shaped the long‐term interaction compositions. Meanwhile, population dynamics, especially species extinction, affected the difference between initial and long‐term interactions. Based on classical consumer–resource theory, these results establish a transitional continuum of interaction outcomes in ecological networks and imply a theoretical association among interaction transition, community persistence and interaction diversity. 相似文献