Comparison and Effects of Acute Lamotrigine Treatment on Extracellular Excitatory Amino Acids in the Hippocampus of PTZ-Kindled Epileptic and PTZ-Induced Status Epilepticus Rats

In this communication, the effect of acute treatment with lamotrigine (LTG) was investigated on release of main excitatory amino acids (EAA) such as glutamate (Glu) and aspartate (Asp) in the hippocampus of pentylenetetrazol (PTZ)-induced and PTZ-kindled freely moving rats using micro dialysis. The results show that, levels of Glu and Asp significantly increased in the rat hippocampus during the seizure/interical periods for PTZ-status epilepticus (SE) and PTZ-kindled epileptic (EP) rats. The levels of Glu and Asp increased more in EP rat hippocampus than in SE rat hippocampus. After administration of 20 mg/kg LTG, the levels of Glu and Asp significantly decreased in the SE and EP rat hippocampus. The results indicate that: (a) excitability of the PTZ-kindled epileptogenic model is higher than that of the status epilepticus model; (b) the modulation of LTG on the EAA neurotransmitters certainly plays an important role in antiepileptic efficacy, especially in PTZ-kindled epileptic model where the release of EAA was influenced more markedly by acute application of 20 mg/kg LTG.     

军医大学学员坚毅性评价的内隐效应及脑电特征研究

目的:探寻军医大学学员内隐层面对自我和他人坚毅性评价的特点及脑电特征,为全面、客观的评估个体的坚毅性提供理论依据和客观指标。方法:使用E-Prime2.0参照经典内隐联想范式编制内隐联想-坚毅测验,对100名军医大学学员施测坚毅量表(Grit O),选取高、低坚毅水平被试(各20名)进行内隐联想-坚毅测验,并记录脑电,分析两组被试的内隐效应及主要脑电成分。结果:计算内隐效应D值,t检验显示高坚毅组(0.55±0.36)显著低于低坚毅组(0.87±0.49),t=-2.257,P0.05,Cohen'd=0.74。两组被试均诱发明显的N400和LPP,高坚毅组中N400在任务状态下主效应显著,F(1,17)=8.528,P0.05,η2=0.334,且在电极位置上主效应显著,F(10,170)=8.207,P0.001,η2=0.326。LPP在任务状态下主效应显著,F(1,17)=5.471,P0.05,η2=0.243,且在电极位置上主效应显著,F(10,170)=18.479,P0.001,η2=0.521;低坚毅组中N400在任务状态下主效应显著,F(1,17)=10.051,P0.05,η2=0.372,且在电极位置上主效应显著,F(10,170)=8.223,P0.001,η2=0.326,LPP在任务状态下主效应不显著。结论:1.军医大学学员坚毅性评价的内隐效应显著,即均倾向于认为自我的坚毅性高,他人的坚毅性低,通过问卷法评估坚毅性时应考虑坚毅评价的内隐效应。2.高、低坚毅性军医大学学员坚毅性内隐评价时的主要脑电成分N400、LPP存在差异,N400可作为坚毅性内隐评价符合程度的判断指标。3.内隐效应及N400可以作为对军医大学学员坚毅性评价时的客观指标。     

Differential effects of paraoxonase 1 (PON1) polymorphisms on cancer risk: evidence from 25 published studies

Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stress, which is thought to contribute to cancer development. PON1 activity varies widely among individuals, which is in part related to two common nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M). The polymorphisms in PON1 have been implicated in cancer risk. However, results from the studies to date have been conflicting. To clarify the association, a meta-analysis was performed for 7,073 cases and 9,520 controls from 25 published case–control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Significant associations between PON1-L55M but not Q192R polymorphism and total cancer were observed from all the comparisons. In stratified analyses, PON1-55M allele was a risk factor for breast cancer. Similarly, increased risk was observed for prostate cancer (OR = 1.18, 95% CI: 1.01–1.36, P _{heterogeneity} = 0.260) and Caucasian population (OR = 1.18, 95% CI: 1.02–1.38, P _{heterogeneity} = 0.1) of the LM genotype, compared with the LL genotype. For PON1-Q192R polymorphism, PON1-192R allele was a decreased risk factor for cancer in the Asian group (RR vs QQ: OR = 0.61, 95% CI: 0.38–0.98, P _{heterogeneity} = 0.268; QR vs QQ: OR = 0.71, 95% CI: 0.52–0.96, P _{heterogeneity} = 0.130; RR + QR vs QQ: OR = 0.71, 95% CI: 0.53–0.95, P _{heterogeneity} = 0.135). Although some modest bias could not be eliminated, this meta-analysis suggests that the PON1-55M allele is a risk factor for the development of cancer, in particular for breast cancer. Future studies with larger sample sizes are warranted to further evaluate these associations.     

Improving rice yield and quality by QTL pyramiding

To facilitate marker-assisted transfer of desirable genes for improvement of yield traits, we used a set of backcross recombinant inbred lines (BRIL) derived from two elite parental lines, ‘Zhenshan97’ and ‘93-11’, to resolve a quantitative trait loci (QTL) cluster for heading date and yield-related traits in rice. Four main-effect QTL (qHD6.1, qHD6.2, qHD7, and qHD8) and four epistatic QTL affecting heading date in the BRIL were detected in two experimental trials. The major QTL (qHD8) was confirmed in three heterogeneous inbred families (HIF) that segregated for this target region, and narrowed down to a 20-kb segment in a large HIF-derived population. qHD8 was found to interact with qHD7 and had a pleiotropic effect responsible for heading date and yield components. To test usability of the identified QTL in rice improvement, we further developed near-isogenic lines (NIL) containing one or more target genes by marker-assisted transfer of ‘93-11’ alleles at qHD8, qHD7, and qHD6.1, and the GS3 gene for grain size into ‘Zhenshan97’. The pyramid line NIL(qHD8 + GS3) had higher yield potential, longer grains, and a more suitable heading date than ‘Zhenshan97’. Comparison of the NIL showed existence of epistasis between alleles at different loci and background effect on qHD8, which are very important for pyramiding of desirable alleles at the target QTL. These results will be particularly useful not only to understand the genetic basis of yield-related traits but also to improve the efficiency of marker-assisted selection for favorable loci in rice breeding programs.     

Activation of NF-κB in CD8+ dendritic cells Ex Vivo by the γ134.5 null mutant correlates with immunity against herpes simplex virus 1

The γ₁34.5 protein of herpes simplex viruses (HSV) is essential for virulence. Accordingly, an HSV mutant lacking γ₁34.5 is attenuated in vivo. Despite its vaccine potential, the mechanism by which the γ₁34.5 null mutant triggers protective immunity is unknown. In this report we show that vaccination with the γ₁34.5 null mutant protects against lethal challenge from wild-type virus via IκB kinase in dendritic cells (DCs), which sense virus-associated molecular patterns. Unlike mock-treated DCs, DCs primed with the γ₁34.5 null mutant ex vivo mediate resistance to wild-type HSV after adoptive transfer into naïve mice. Furthermore, the γ₁34.5 null mutant activates IκB kinase, which facilitates p65/RelA phosphorylation and nuclear translocation, resulting in DC maturation. While unable to produce infectious virus in DCs, this mutant virus expresses early and late genes. In its abortive infection, the γ₁34.5 null mutant induces protective immunity more effectively in CD8⁺ DCs than in CD8⁻ DCs. This is mirrored by a higher level of interleukin-6 (IL-6) and IL-12 secretion by CD8⁺ DCs than CD8⁻ DCs. Remarkably, inhibition of p65/RelA phosphorylation or nuclear translocation in CD8⁺ DCs disrupts protective immunity. These results suggest that engagement of the γ₁34.5 null mutant with CD8⁺ DCs elicits innate immunity to activate NF-κB, which translates into protective immunity.     

A new kinosternoid from the Late Cretaceous Hell Creek Formation of North Dakota and Montana and the origin of the <Emphasis Type="Italic">Dermatemys mawii</Emphasis> lineage

A nearly complete turtle shell from the Late Cretaceous (Maastrichtian) Hell Creek Formation of Slope County, North Dakota, represents the most complete remains to date of a Mesozoic kinosternoid turtle and a new species, Hoplochelys clark nov. sp. The new taxon is diagnosable from other representatives of Hoplochelys by the plesiomorphic placement of the humeral/femoral sulcus behind the hyo/hypoplastral suture and the autapomorphic development of an interrupted median (neural) keel. All six previously named Paleocene (Puercan and Torrejonian) representatives of Hoplochelys lack diagnostic characters and are synonymized as Hoplochelys crassa. A phylogenetic analysis reveals that Hoplochelys spp. and Agomphus pectoralis are most parsimoniously placed within Kinosternoidea along the phylogenetic stem of the extant Mesoamerican River Turtle Dermatemys mawii, extending that taxon’s stem lineage from the early Eocene to the late Maastrichtian. The two primary crown lineages of Kinosternoidea are thus known from the Mesozoic and split prior to the late Campanian. The presence of a thickened cruciform plastron, true costiform processes, only three inframarginals, and the reduction of the medial contact of the abdominals are synapomorphies of Chelydroidea, the clade formed by Chelydridae and Kinosternoidae.     

Xenoestrogenic short ethoxy chain nonylphenol is oxidized by a flavoprotein alcohol dehydrogenase from <Emphasis Type="Italic">Ensifer</Emphasis> sp. strain AS08

The ethoxy chains of short ethoxy chain nonylphenol (NPEO_av2.0, containing average 2.0 ethoxy units) were dehydrogenated by cell-free extracts from Ensifer sp. strain AS08 grown on a basal medium supplemented with NPEO_av2.0. The reaction was coupled with the reduction in 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and phenazine methosulfate. The enzyme (NPEO_av2.0 dehydrogenase; NPEO-DH) was purified to homogeneity with a yield of 20% and a 56-fold increase in specific activity. The molecular mass of the native enzyme was 120 kDa, consisting of two identical monomer units (60 kDa). The gene encoding NPEO-DH was cloned, which consisted of 1,659 bp, corresponding to a protein of 553 amino acid residues. The deduced amino acid sequence agreed with the N-terminal amino acid sequence of the purified NPEO-DH. The presence of a flavin adenine dinucleotide (FAD)-binding motif and glucose–methanol–choline (GMC) oxidoreductase signature motifs strongly suggested that the enzyme belongs to the GMC oxidoreductase family. The protein exhibited homology (40–45% identity) with several polyethylene glycol dehydrogenases (PEG-DHs) of this family, but the identity was lower than those (approximately 58%) among known PEG-DHs. The substrate-binding domain was more hydrophobic compared with those of glucose oxidase and PEG-DHs. The recombinant protein had the same molecular mass as the purified NPEO-DH and dehydrogenated PEG400-2000, NPEO_av2.0 and its components, and NPEOav10, but only slight or no activity was found using diethylene glycol, triethylene glycol, and PEG200. English edition: The paper was edited by a native speaker through American Journal Experts ().     

Hepatitis C virus inhibits AKT-tuberous sclerosis complex (TSC), the mechanistic target of rapamycin (MTOR) pathway,through endoplasmic reticulum stress to induce autophagy

Hepatitis C virus (HCV) is able to induce autophagy via endoplasmic reticulum (ER) stress, but the exact molecular signaling pathway is not well understood. We found that the activity of the mechanistic target of rapamycin complex 1 (MTORC1) was inhibited in Huh7 cells either harboring HCV-N (genotype 1b) full-genomic replicon or infected with JFH1 (genotype 2a) virus, which led to the activation of UNC-51-like kinase 1 (ULK1) and thus to autophagy. We then analyzed activity upstream of MTORC1, and found that both protein kinase, AMP-activated, α (PRKAA, including PRKAA1 and PRKAA2, also known as AMP-activated protein kinase, AMPKα) and AKT (refers to pan AKT, including three isoforms of AKT1-3, also known as protein kinase B, PKB) were inhibited by HCV infection. The inhibition of the AKT-TSC-MTORC1 pathway contributed to upregulating autophagy, but inhibition of PRKAA downregulated autophagy. The net effect on autophagy was from AKT, which overrode the inhibition effect from PRKAA. It was further found that HCV-induced ER stress was responsible for the inhibition of the AKT pathway. Metformin, a PRKAA agonist, inhibited HCV replication not only by activating PRKAA as previously reported, but also by activating AKT independently of the autophagy pathway. Taken together, our data suggested HCV inhibited the AKT-TSC-MTORC1 pathway via ER stress, resulting in autophagy, which may contribute to the establishment of the HCV-induced autophagy.