Gas-phase reactions of ClO–/BrO– with RCl (R = CH3, C2H5, and C3H7) have been investigated in detail using the popular DFT functional BHandHLYP/aug-cc-pVDZ level of theory. As a result, our findings strongly suggest that the type of reaction is firstly initiated by a typical SN2 fashion. Subsequently, two competitive substitution steps, named as SN2-induced substitution and SN2-induced elimination, respectively, would proceed before the initial SN2 product ion-dipole complex separates, in which the former exhibits less reactivity than the latter. Those are consistent with relevant experimental results. Moreover, we have also explored reactivity difference for the title reactions in term of some factors derived from methyl group, p-π electronic conjugation, ionization energy (IE), as well as molecular orbital (MO) analysis.
Figure
Energy profiles for the ClO– reactions and BrO–reactions, respectively 相似文献
In 2006, Dr Shinya Yamanaka succeeded to reprogram somatic cells into pluripotent stem cells (iPSC) by delivering the genes encoding Oct4, Sox2, Klf4, and c-Myc. This achievement represents a fundamental breakthrough in stem cell biology and opens up a new era in regenerative medicine. However, the molecular processes by which somatic cells are reprogrammed into iPSC remain poorly understood. In 2009, Yamanaka proposed the elite and stochastic models for reprogramming mechanisms. To date, many investigators in the field of iPSC research support the concept of stochastic model, i.e., somatic cell reprogramming is an event of epigenetic transformation. A mathematical model, f (Cd, k), has also been proposed to predict the stochastic process. Here we wish to revisit the Yamanaka model and summarize the recent advances in this research field. 相似文献
A dynamic model called hybrid cybernetic model (HCM) based on structured metabolic network is established for simulating mammalian cell metabolism featured with partially substitutable and partially complementary consumption patterns of two substrates, glucose and glutamine. Benefiting from the application of elementary mode analysis (EMA), the complicated metabolic network is decomposed into elementary modes (EMs) facilitating the employment of the hybrid cybernetic framework to investigate the external and internal flux distribution and the regulation mechanism among them. According to different substrate combination, two groups of EMs are obtained, i.e., EMs associated with glucose uptake and simultaneous uptake of glucose and glutamine. Uptake fluxes through various EMs are coupled together via cybernetic variables to maximize substrate uptake. External fluxes and internal fluxes could be calculated and estimated respectively, by the combination of the stoichiometrics of metabolic networks and fluxes through regulated EMs. The model performance is well validated via three sets of experimental data. Through parameter identification of limited number of experimental data, other external metabolites are precisely predicted. The obtained kinetic parameters of three experimental cultures have similar values, which indicates the robustness of the model. Furthermore, the prediction performance of the model is successfully validated based on identified parameters. 相似文献
Abstract Neutralization of tumor necrosis factor‐α (TNF‐α) has become an effective therapeutic strategy for TNF‐related autoimmune diseases. Due to the limitations of the large molecular inhibitors in the therapy, development of novel TNF‐α inhibitors is very attractive and useful. In this study, based on the previously designed domain antibody, two novel human anti‐TNF single‐chain antibodies were constructed using modular consensus frameworks of human antibody as scaffold to display the antagonistic peptides. A variety of expression plasmids were used to determine the optimal expression system. The single‐chain antibodies were always overexpressed in E.coli BL21(DE3) host as inclusion bodies. Under the optimized refolding conditions, the inclusion bodies were renatured successfully and the refolded single‐chain antibodies could bind with TNF‐α and block TNF‐induced cytotoxicity on L929 cells. The bioactivity of the single‐chain antibodies was significantly increased over the domain antibody. 相似文献
The biodegradation of high concentration isopropanol (2-propanol, IPA) at 16 g/L was investigated by a solvent-tolerant strain of bacteria identified as Paracoccus denitrificans for the first time by 16S rDNA gene sequencing. The strain P. denitrificans GH3 was able to utilize the high concentration of IPA as the sole carbon source within a minimal salts medium with a cell density of 1.5 × 108 cells/mL. The optimal conditions were found as follows: initial pH 7.0, incubation temperature 30°C, with IPA concentration 8 g/L. Under the optimal conditions, strain GH3 utilized 90.3% of IPA in 7 days. Acetone, the major intermediate of aerobic IPA biodegradation, was also monitored as an indicator of microbial IPA utilization. Both IPA and acetone were completely removed from the medium following 216 hr and 240 hr, respectively. The growth of strain GH3 on IPA as a sole carbon and energy source was well described by the Andrews model with a maximum growth rate (μmax) = 0.0277/hr, a saturation constant (KS) = 0.7333 g/L, and an inhibition concentration (Ki) = 8.9887 g/L. Paracoccus denitrificans GH3 is considered to be well used in degrading IPA in wastewater. 相似文献
The hexanucleotide repeat expansion, GGGGCC (G4C2), within the first intron of the C9orf72 gene is known to be the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The G4C2 repeat expansions, either DNA or RNA, are able to form G-quadruplexes which induce toxicity leading to ALS/FTD. Herein, we report a novel crystal structure of d(G4C2)2 that self-associates to form an eight-layer parallel tetrameric G-quadruplex. Two d(G4C2)2 associate together as a parallel dimeric G-quadruplex which folds into a tetramer via 5′-to-5′ arrangements. Each dimer consists of four G-tetrads connected by two CC propeller loops. Especially, the 3′-end cytosines protrude out and form C·C+•C·C+/ C·C•C·C+ quadruple base pair or C•C·C+ triple base pair stacking on the dimeric block. Our work sheds light on the G-quadruplexes adopted by d(G4C2) and yields the invaluable structural details for the development of small molecules to tackle neurodegenerative diseases, ALS and FTD. 相似文献
This study aimed to explore the effects and function of microRNA-101a-3p (miR-101a-3p) in epilepsy. Rat model of pilocarpine-induced epilepsy was established and the seizure frequency was recorded. Expression of miR-101a-3p and c-Fos in hippocampus tissues of Rat models were detected by qRT-PCR and western blot. Besides, we established a hippocampal neuronal culture model of acquired epilepsy using Mg2+ free medium to evaluate the effects of miR-101a-3p and c-Fos in vitro. Cells were transfected with miR-101a-3p mimic, si-c-FOS, miR-101a-3p?+?c-FOS and its corresponding controls. MTT assay was used to detect cell viability upon transfection. Flow cytometry was performed to determine the apoptosis rate. Western blot was performed to measure the protein expression of apoptosis-related proteins (Bcl-2, Bax, and cleaved caspase 3), autophagy-related proteins (LC3 and Beclin1) and c-FOS. The targeting relationship between miR-101a-3p and c-FOS was predicted and verified by TargetScan software and dual-luciferase reporter assay. The role of miR-101a-3p was validated using epilepsy rat models in vivo. Another Rat models of pilocarpine-induced epilepsy with miR-NC or miR-101a-3p injection were established to evaluate the effect of miR-101a-3p overexpression on epilepsy in vivo. MiR-101a-3p was downregulated while c-FOS was increased in hippocampus tissues of Rat model of pilocarpine-induced epilepsy. Overexpression of miR-101a-3p or c-FOS depletion promoted cell viability, inhibited cell apoptosis and autophagy. C-FOS was a target of miR-101a-3p and miR-101a-3p negatively regulated c-FOS expression to function in epilepsy. Overexpression of miR-101a-3p attenuated pilocarpine-induced epilepsy in Rats in vivo. This study indicated that miR-101a-3p could attenuate pilocarpine-induced epilepsy by repressing c-Fos expression.