Modelling HIV immune response and validation with clinical data

A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain features that have been shown to be important by recent experimental research are incorporated in the model. These include the role of CD4+memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria. We show that this more biologically detailed model can exhibit the phenomenon of transient viremia experienced by some patients on therapy with viral load levels suppressed below the detection limit. We also show that the loss of CD4+T-cell help in the generation of CD8+memory cells leads to larger peak values for the viral load during transient viremia. Censored clinical data is used to obtain parameter estimates. We demonstrate that using a reduced set of 16 free parameters, obtained by fixing some parameters at their population averages, the model provides reasonable fits to the patient data and, moreover, that it exhibits good predictive capability. We further show that parameter values obtained for most clinical patients do not admit multiple locally a.s off-treatment equilibria. This suggests that treatment to move from a high viral load equilibrium state to an equilibrium state with a lower (or zero) viral load is not possible for these patients.     

Neuroprotective effects of extract of Acanthopanax senticosus harms on SH-SY5Y cells overexpressing wild-type or A53T mutant α-synuclein

Extract of Acanthopanax senticosus harms (EAS) has been shown to have neuroprotective effects on dopaminergic neurons in Parkinson's disease (PD) mice model. α-Synuclein is a key player in the pathogenesis of PD, the elevated level of which is deleterious to dopaminergic neurons, and enhancing its clearance might be a promising strategy for treating PD. To assess the potential of EAS in this regard, we investigated its effect on the SH-SY5Y cells overexpressing wild-type α-synuclein (WT-α-Syn) or A53T mutant α-synuclein (A53T-α-Syn), and the implicated pathway it might mediate. After treatment with EAS, the changes of α-synuclein, caspase-3, parkin, phospho-protein kinase B (Akt), phospho-glycogen synthase kinase 3 beta (GSK3β), and phospho-microtubule-associated protein tau (Tau) in WT-α-Syn or A53T-α-Syn transgenic cells were reverted back to near normal levels, demonstrated by the western blotting and quantitative real-time PCR outcomes. The neuroprotective effects of EAS may be able to protect WT-α-Syn or A53T-α-Syn transgenic SH-SY5Y cells from α-synuclein overexpression and toxicity. Therefore, we speculate that EAS might be a promising candidate for prevention or treatment of α-synuclein-related neurodegenerative disorders such as PD.     

Characterization of tubule and monomer derived from VP4 protein of infectious bursal disease virus

The VP4 protein of infectious bursal disease virus (IBDV) is a serine protease that processes the polyprotein for viral assembly. VP4 has been found to associate primarily with type II IBDV tubules that are 24 nm in diameter. In this study, a chimeric VP4, assigned as HS1VP4, was constructed with a VP4-autocleavage site inserted between the N-terminal His-tag and the VP4 sequence. The results showed that the VP4 forms tubules after the self-cleavage of HS1VP4 when expressed in Escherichia coli. Furthermore, a deletion of 28 amino acids at the C-terminus of VP4 resulted in monomers and dimers instead of tubule formation; mutants of S652A and K692A at active site destroyed the activity. The endopeptidase activity of these monomers and dimers was approximately 12.5 times higher than that of VP4 tubules. Additionally, the formation of tubules inhibited VP4 protease activity, as demonstrated through in vitro assays. The production and characterization of monomers or dimers that have greater endopeptidase activity and protease activity than tubules can provide further insight into VP4 tubule assembly and the regulation of VP4 activity in host cells; this insight will facilitate the development of new anti-IBDV strategies.     

An actuated dissipative spring-mass walking model: Predicting human-like ground reaction forces and the effects of model parameters

Simple models are widely used to understand the mechanics of human walking. The optimization-based minimal biped model and spring-loaded-inverted-pendulum (SLIP) model are two popular models that can achieve human-like walking patterns. However, ground reaction forces (GRF) from these two models still deviate from experimental data. In this paper, we proposed an actuated dissipative spring-mass model by integrating these two models to realize more human-like GRF patterns. We first explored the function of stiffness, damping, and weights of both energy cost and force cost in the objective function and found that these parameters have distinctly different influences on the optimized gait and GRF profiles. The stiffness and objective weight affect the number and size of peaks in the vertical GRF and stance time. The damping changes the relative size of the peaks but has little influence on stance time. Based on these observations, these parameters were manually tuned at three different speeds to approach experimentally measured vertical GRF and the highest correlation coefficient can reach 0.983. These results indicate that the stiffness, damping, and proper objective functions are all important factors in achieving human-like motion for this simple walking model. These findings can facilitate the understanding of human walking dynamics and may be applied in future biped models.     

A recombinant foot-and-mouth disease virus antigen inhibits DNA replication and triggers the SOS response in Escherichia coli

Abstract The 3D gene of foot-and-mouth disease virus encodes the viral RNA dependent RNA polymerase, also called virus infection associated (VIA) antigen, which is the most important serological marker of virus infection. This 3D gene from a serotype Cl virus has been cloned and overexpressed in Escherichia coli under the control of the strong lambda lytic promoters. The resulting 51 kDa recombinant protein has been shown to be immunoreactive with sera from infected animals. After induction of gene expression, an immediate and dramatic arrest of cell DNA synthesis occurs, similar to that produced by genotoxic doses of the drug mitomycin C. This effect does not occur during the production of either a truncated VIA antigen or other related and non-related viral proteins. The inhibition of DNA replication results in a subsequent induction of the host SOS DNA-repair response and in an increase of the mutation frequency in the surviving cells.     

Synthesis,molecular docking,acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease

A series of thirty (30) thiazole analogs were prepared, characterized by ¹H NMR, ¹³C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC₅₀ value ranging between 1.59 ± 0.01 and 389.25 ± 1.75 μM when compared with the standard eserine (IC₅₀, 0.85 ± 0.0001 μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC₅₀ values 1.59 ± 0.01, 1.77 ± 0.01, 6.21 ± 0.01, 7.56 ± 0.01, 8.46 ± 0.01, 14.81 ± 0.32 and 16.54 ± 0.21 μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3 ± 0.50, 35.3 ± 0.64, 36.6 ± 0.70, 44.81 ± 0.81, 46.36 ± 0.84, 48.2 ± 0.06 and 48.72 ± 0.91 μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking.     

重庆市生态风险预警等级划分及演化趋势模拟

生态风险预警等级评估和演化趋势模拟，可为生态风险管理提供可靠的辅助决策。以重庆市为研究对象，基于驱动力-压力-状态-影响-响应模型，构建重庆市生态风险预警指标体系，采用正态云模型和集对分析法，定量分析重庆市生态风险时空分异特征和演化趋势。研究结果表明：（1）2013-2019年，重庆市生态风险值呈"上升-下降"的波动趋势，综合生态风险隶属于重警等级，生态风险综合值从0.295下降到0.278，生态环境逐年好转；（2）重庆市生态风险有下降、不变、先上升后降低、先降低后上升以及一直升高5种演化趋势，分别占比39%、16%、5%、21%、24%；（3）重庆市生态风险转移分为两个方向，2013-2016年生态风险空间分异性增大，中警、轻警和无警风险等级不断向东北、东南和西部四周分散转移；2016-2019年生态风险分布格局变化较小，重警风险区在东部聚集；（4）演化趋势模拟结果表明，未来重庆市生态风险降低的区县有13个，占比34%，生态环境有向好发展的趋势；生态风险上升的区县有25个，占比66%，生态环境会有所恶化，但是恶化程度较低。将生态风险等级划分与预警演化趋势相结合，能为城市生态风险管理提供科学依据。     

分泌型磷脂酶PLA2G5的生物学功能及其抑制剂研究进展

分泌型磷脂酶PLA2G5属于磷脂酶A2超家族的一员,在免疫细胞和非免疫细胞中均有表达.研究表明,PLA2G5参与生物学事件的发生发展,在特定的病理条件下具有诱导作用.本文简要阐述了PLA2G5的来源、结构特征、生物学功能和在疾病中的作用,以及现有或潜在的PLA2G5抑制剂,以期探索基于PLA2G5的治疗新靶标.