Role of the APOE ε2/ε3/ε4 Polymorphism in the Development of Primary Open-Angle Glaucoma: Evidence from a Comprehensive Meta-Analysis

Primary open-angle glaucoma (POAG) is one of the leading causes of blindness worldwide. The association between the APOE ε2/ε3/ε4 polymorphism and the risk of POAG has been widely reported, but the results of previous studies remain controversial. To comprehensively evaluate the APOE ɛ2/ɛ3/ε4 polymorphism on the genetic risk for POAG, we performed a systematic review and meta-analysis of previously published studies. The PubMed and Web of Science databases were systematically searched to identify relevant studies. Data were extracted from these studies and odds ratios with corresponding 95% confidence intervals were computed to estimate the strength of the association. Stratified analyses according to ethnicity and sensitivity analyses were also conducted for further confirmation. A total of nine studies were eligible for the meta-analysis, and these studies included data on 1928 POAG cases and 1793 unrelated match controls. The combined results showed that there were no associations between the APOE ε2/ε3/ε4 polymorphism and POAG risk in any of the 10 comparison models. The analysis that was stratified by ethnicity subgroups also failed to reveal a significant association. The sensitivity analysis confirmed the stability and reliability of the findings. There was no risk of publication bias. Our meta-analysis provides strong evidence that the APOE ε2/ε3/ε4 polymorphism is not associated with POAG susceptibility in any populations.     

消炎痛对大鼠肝线粒体微粒体^45Ca摄取及膜流动性的影响

我们曾报道消炎痛预处理在大鼠能引起明显的肝保护作用,为了进一步探讨消炎痛肝保护作用的机制,本工作观察了它对大鼠肝线粒体、微粒体钙调节作用及膜流动性的影响。结果表明,经消炎痛整体预处理的大鼠肝线粒体和微粒体的钙摄取及膜流动性均明显增加,但是,将消炎痛直接加入由正常大鼠分离的线粒体或微粒体中,则反而使膜的流动性降低。这些变化可能与消炎痛的肝保护作用有关。     

Zinc has opposite effects on NMDA and non-NMDA receptors expressed in Xenopus oocytes

Pharmacological characterization of Zn2+ effects on glutamate ionotropic receptors was investigated in Xenopus oocytes injected with rat brain mRNA, using a double microelectrode, voltage-clamp technique. At low concentration, Zn2+ inhibited NMDA currents (IC50 = 42.9 +/- 1.3 microM) and potentiated both AMPA (EC50 = 30.0 +/- 1.2 microM) and desensitized kainate responses (EC50 = 13.0 +/- 0.1 microM). At higher concentrations, Zn2+ inhibited non-NMDA responses with IC50 values of 1.3 +/- 0.1 mM and 1.2 +/- 0.3 mM for AMPA and kainate, respectively. The potentiation of AMPA or quisqualate currents by Zn2+ was more than 2-fold, whereas that of the kainate current was only close to 30%. This potentiating effect of Zn2+ on AMPA current modified neither the affinity of the agonist for its site nor the current-voltage relationship. In addition, 500 microM Zn2+ differentially affected NMDA and non-NMDA components of the glutamate-induced response. The possible physiological relevance of Zn2+ modulation is discussed.     

Maitotoxin-Evoked γ-Aminobutyric Acid Release Is Due Not Only to the Opening of Calcium Channels

The effects of maitotoxin (MTX) on endogenous amino acid release were tested on highly purified striatal neurons differentiated in primary culture. MTX induced a large and concentration-dependent release of gamma-aminobutyric acid (GABA). This effect was abolished when experiments were performed in the absence of external Ca2+, and restored when Ca2+ ions were added after removing the MTX-containing Ca2+-free solution. MTX-induced amino acid release was not affected by 1 microM nifedipine and only slightly inhibited by 1 mM Co2+. MTX also induced a massive accumulation of 45Ca2+ in the neurons which, in contrast to the MTX-evoked GABA release, was totally blocked in the presence of 1 mM Co2+. Whereas 500 nM tetrodotoxin was without significant effect, MTX-evoked GABA release was dependent on the presence of external Na+ and sensitive to nipecotic acid, a GABA uptake inhibitor. It is concluded that, on striatal neurons, MTX induced Na+ influx only in the presence of external Ca2+. The increase in cytoplasmic Na+ ions then triggers the release of GABA.     

Photosynthetic productivity of an immature maize crop: changes in quantum yield of CO2 assimilation, conversion efficiency and thylakoid proteins

Abstract. The effect of growth temperatures on quantum yield (φ) was examined for leaves at different stages of development within the immature canopies of two crops of field grown maize ( Zea mays cv. LG11) sown on 3 May and 20 June 1990. During the period of 23 to 49d after sowing, the crop sown on the 3 May experienced temperatures below 10°C on 19 occasions compared with only two for the crop sown on 20 June. A period of severe chilling at the end of May and the beginning of June was associated with a marked reduction in φ for all leaves in the early-sown crop. This chill-induced depression in φ was greater in recently emerged than more mature leaves in the canopy and was found to be accompanied by modifications in the polypeptide profiles of thylakoids isolated from the leaves. During the chilling period, decreases in some polypeptides, notably in the range of 41–42 and 20kDa apparent molecular size, and increases of polypeptides of c. 15–16kDa were observed compared with leaves developing at warmer temperatures in July. The efficiency of converting intercepted radiation into dry matter (conversion efficiency) was 42% lower in the early- than late-sown crop, but no significant relationship between conversion efficiency and quantum yield was found in either treatment.     

The metabotropic glutamate receptor (MGR): pharmacology and subcellular location.

A pharmacological characterization of the metabotropic glutamate receptor (MGR) was performed in striatal neurons. Among the excitatory amino acid receptor antagonists tested, only D, L-2-amino-3-phosphonopropionate (D, L-AP3) inhibited QA-induced inositol phosphate (InsP) formation in a competitive manner (mean pKi = 4.45 +/- 0.43, n = 4). However, this drug was a partial agonist of MGR since it stimulated the inositol-phosphate formation. We found that D, L-AP3 also inhibited NMDA-induced calcium increase, in a competitive manner (mean pIC50 = 4.34 +/- 0.22, n = 8, and mean pKi = 3.7 +/- 0.11 n = 5). 1 mM of the ionotropic agonists alpha-amino-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate (KA) or domoate (DO) (100 microM or higher) induced a significant InsP formation in striatal neurons. The InsP responses induced by all these agonists were totally blocked by the phorbol ester phorbol-12,13-dibutyrate (PdBu), but not by atropine or prazosin. Agonist-induced increases of intracellular calcium concentrations ([Ca2+]i) were insensitive to PdBu, suggesting that all these substances were able to stimulate the MGR in striatal neurons. Trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) evoked dose-dependent inositol phosphate formations with an EC50 of 29 microM but had no significant effect on NMDA or AMPA receptors, as measured by the patch clamp technique. In the presence of 30 microM of AMPA, trans-ACPD induced a significant release of arachidonic acid (AA) in striatal neurons. No important AA release was observed by any of these agonists alone. 56 mM K+ did not mimic AMPA in this associative ionotropic/metabotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Release of Endogenous Amino Acids from Striatal Neurons in Primary Culture

Following partial purification, the characteristics of a cytosol protein kinase were investigated. The protein kinase was purified by ammonium sulfate precipitation and diethylaminoethyl-cellulose, ATP-agarose, and hydroxyapatite chromatography. Analysis of the purified protein kinase preparation by polyacrylamide gel electrophoresis revealed three major protein bands. The cytosol protein kinase was purified approximately 442-fold, as calculated from the cyclic nucleotide independent protein kinase activity in the 40,000 g supernatant. The activity of the kinase was found to be independent of either cyclic AMP or cyclic GMP. Moreover, the kinase activity was unaffected by the addition of the endogenous protein kinase inhibitor, or the regulatory subunit from the type II cyclic AMP-dependent protein kinase from bovine heart. The molecular weight of the enzyme was determined to be 95,000 by Sephadex G-200 gel filtration. The activity of the kinase was increased approximately twofold in the presence of 10 microM Ca+2 and calmodulin. This increase was reversed by the addition of EGTA. The subcellular distribution of the protein kinase was also examined. The soluble fraction from nerve terminal was found to have the highest concentration of the kinase activity.     

The C-Terminal Domain of the mGluR1 Metabotropic Glutamate Receptor Affects Sensitivity to Agonists

Abstract: The metabotropic glutamate receptor (mGluR) subtype 1 exists as at least three variants (−1a, −1b, and −1c) generated by alternative splicing at the C-terminal domain. Fluorometric Ca²⁺ measurements were used to compare the concentration dependency of agonist-induced rises in intracellular free Ca²⁺ concentration ([Ca²⁺]_i) in human embryonic HEK 293 cells transiently expressing rat mGluR1a, mGluR1b, or mGluR1c. The rank order of agonist potencies was quisqualate ≫ (2 S, 1' S, 2' S )-2-(carboxycyclopropyl)glycine (L-CCG-I) > (1 S, 3 R )-1-aminocyclopentane-1,3-dicarboxylic acid [(1 S, 3 R )-ACPD] and did not differ among the splice variants. However, agonists were consistently more potent at mGluR1a than at mGluR1c and mGluR1b. In the same system, we characterized the agonist pharmacology of two chimeric rat mGluR3/1 receptors where the first and/or the second intracellular loop(s) and the C-terminal domain were exchanged with the corresponding mGluR1a or mGluR1c sequences and that were previously shown to mediate elevations in [Ca²⁺]_i in response to agonists. The potency of agonists was higher at the chimera having the C-terminus of mGluR1a as compared with those having the mGluR1c C-terminus. Both chimeric mGluR3/1 receptors had the same rank order of agonist potencies: L-CCG-I ≫ (1 S, 3 R )-ACPD ∼ quisqualate. These data support the hypothesis that the C-terminal domain of mGluRs plays a role in determining the potency of agonists for inducing mGluR-mediated functional responses.     

星花绣线菊中的一个新二萜——绣线菊内酯B

从星花绣线菊（Ｓｐｉｒａｅａｊａｐｏｎｉｃａｖａｒ．ｓｔｅｌｌａｒｉｓ）根中得到１个新的Ａｔｉｓｉｎｅ型二萜,命名为绣线菊内酯Ｂ（１）。通过光谱分析测定了其结构,此外还得到了９个已知化合物,包括１个ａｔｉｓｉｎｅ型二萜－ｓｐｉｒａｍｉｎｏｌ（２）和８个二萜生物碱,ｓｐｉｒａｍｉｎｅＡ,Ｂ,Ｃ,Ｄ,Ｆ,Ｈ,Ｐ,Ｑ。