Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism

NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton flux supporting the operation of NADPH-regenerating enzyme and offers flexibility in coping with NADPH demand for varied intracellular environment. To acquire an insightful understanding of its NADPH regeneration capacity, the elementary mode method was employed to compute all elementary flux modes (EFMs) of a network representative of central carbon metabolism. Based on the metabolic flux distributions of these modes, a cluster analysis of EFMs with high NADPH regeneration rate was conducted using the self-organizing map clustering algorithm. The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme. The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report. Meanwhile, the reaction combinations showed some common characteristics: there were one or two decarboxylation oxidation reactions in the combinations that produced NADPH and the combination constitution included certain gluconeogenesis pathways. These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.     

人参茎叶皂甙对高胆固醇饮食大鼠再灌注性心律失常和脂质过氧化的影响(英文)

研究人参茎叶皂甙(GSL)对高胆固醇饮食大鼠心肌再灌注性心律失常(RPA_r)和脂质过氧化的影响。方法:将胆固醇乳剂用灌胃法饲养大鼠14d,建立高脂血症模型,各组大鼠进行心肌缺血再灌注实验,观察高脂血症和GSL对大鼠心肌缺血再灌注2h后血丙二醇(MDA),超氧化物歧化酶(SOD)和一氧化氮(NO)水平的影响和对再灌注性心律失常发生率的影响。结果显示:(1)用胆固醇乳剂饲养大鼠14d,成功建立高脂血症模型。同时给予GSL14d有明显降脂作用。(2)高脂血症状态下,心肌缺血再灌注2h后,血MDA升高(p<0.01),SOD降低(p<0.01)和NO(p<0.05)降低,再灌注10min内RPAr的发生率增高。(3)GSL组再灌注后2h的血MDA降低,而SOD和NO水平显著升高;使RPAr发生率大为降低,无VF发生。实验显示高脂血症加重心肌缺血再灌注损伤和提高RPAr发生率及动物死亡率,GSL可减少高脂饮食大鼠脂质过氧化和诱导体内NO生成而减轻缺血再灌注心肌损伤,降低缺血再灌注性心律失常发生率。     

Photomutagenicity of 16 polycyclic aromatic hydrocarbons from the US EPA priority pollutant list

The photomutagenicity of 16 polycyclic aromatic hydrocarbons (PAHs), all on the United States Environmental Protection Agency (US EPA) priority pollutant list, was studied. Concomitant exposing the Salmonella typhimurium bacteria strain TA102 to one of the PAHs and light (1.1 J/cm2 UVA+2.1 J/cm2 visible) without the activation enzyme S9, strong photomutagenic response is observed for anthracene, benz[a]anthracene, benzo[ghi]perylene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, and pyrene. Under the same conditions, acenaphthene, acenaphthylene, benzo[k]fluoranthene, chrysene, and fluorene are weakly photomutagenic. Benzo[b]fluoranthene, fluoranthene, naphthalene, phenanthrene, and dibenz[a,h]anthracene are not photomutagenic. These results indicate that PAHs can be activated by light and become mutagenic in Salmonella TA102 bacteria. At the same time, the mutagenicity for all the 16 PAHs was examined with the standard mutagenicity test with 10% S9 as the activation system. Benzo[b]fluoranthene, benzo[k]fluoranthene, chrysene, acenaphthylene, and fluorene are weakly mutagenic, while the rest of the PAHs are not. In general, the photomutagenicity of PAHs in TA102 does not correlate with their S9-activated mutagenicity in either TA102 or TA98/TA100 since they involve different activation mechanisms.     

NF-kappaB protects macrophages from lipopolysaccharide-induced cell death: the role of caspase 8 and receptor-interacting protein

Macrophages play a pivotal role in the pathogenesis of a variety of diseases. These studies were performed to characterize the mechanisms by which Toll-like receptor 4 (TLR4)-mediated NF-kappaB activation promotes resistance to cell death in macrophages. When NF-kappaB activation was inhibited by a super-repressor, IkappaBalpha, the TLR4 ligand lipopolysaccharide induced the activation of caspase 8, the loss of mitochondrial transmembrane potential (DeltaPsim), and apoptotic cell death in macrophages. The inhibition of caspase 8 activation suppressed DNA fragmentation but failed to protect macrophages against the loss of DeltaPsim and resulted in necrotic cell death. In contrast, the reduction of receptor-interacting protein 1 suppressed the loss of DeltaPsim and inhibited apoptotic cell death. Further, when caspase 8 activation was suppressed, the knock down of receptor-interacting protein inhibited the loss of DeltaPsim and necrotic cell death. These observations demonstrate that following TLR4 ligation by lipopolysaccharide, NF-kappaB is a critical determinant of macrophage life or death, whereas caspase 8 determines the pathway employed.     

A novel real-time driving fatigue detection system based on wireless dry EEG

Development of techniques for detection of mental fatigue has varied applications in areas where sustaining attention is of critical importance like security and transportation. The objective of this study is to develop a novel real-time driving fatigue detection methodology based on dry Electroencephalographic (EEG) signals. The study has employed two methods in the online detection of mental fatigue: power spectrum density (PSD) and sample entropy (SE). The wavelet packets transform (WPT) method was utilized to obtain the \(\theta \) (4–7 Hz), \(\alpha \) (8–12 Hz) and \(\beta \) (13–30 Hz) bands frequency components for calculating corresponding PSD of the selected channels. In order to improve the fatigue detection performance, the system was individually calibrated for each subject in terms of fatigue-sensitive channels selection. Two fatigue-related indexes: (\(\theta +\alpha \))/\(\beta \) and \(\theta \)/\(\beta \) were computed and then fused into an integrated metric to predict the degree of driving fatigue. In the case of SE extraction, the mean of SE averaged across two EEG channels (‘O1h’ and ‘O2h’) was used for fatigue detection. Ten healthy subjects participated in our study and each of them performed two sessions of simulated driving. In each session, subjects were required to drive simulated car for 90 min without any break. The results demonstrate that our proposed methods are effective for fatigue detection. The prediction of fatigue is consistent with the observation of reaction time that was recorded during simulated driving, which is considered as an objective behavioral measure.