Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency

Glycosylation, an important post-translation modification, could alter biological activity or influence the clearance rates of glycoproteins. We report here the first example of a heterozygous protein deficiency leading to metabolic alteration of N-glycan structures in residual secreted protein. Analysis of C1 esterase inhibitor (C1INH) glycans from normal individuals and patients with hereditary deficiency of C1INH demonstrated identical O-glycan structures but the N-glycans of patients with a heterozygous genetic deficiency were small, highly charged and lacked sialidase releasable N-acetylneuraminic acid. Structural studies indicate that the charge character of these aberrant N-glycan structures may result from the presence of mannose-6-phosphate residues. These residues might facilitate secretion of C1INH through an alternate lysosomal pathway, possibly serving as a compensatory mechanism to enhance plasma levels of C1INH in these deficient patients.     

胰高血糖素样肽1受体--治疗糖尿病新药的研究热点

胰高血糖素样肽l(glucagon—like peptide—l,GLP-1)与胰岛素分泌和糖代谢调节密切相关。GLP-1与其受体(GLP-1receptor,GLP-1R)结合后,主要通过cAMP和P13K两条信号途径,促进胰岛素的分泌,刺激胰岛β细胞的增殖和分化。对GLP-1R结构和信号传导机制的研究,有助于了解其在糖尿病病理进程中的作用,为开发新型糖尿病治疗药物指明方向。     

渗滤液溶解性有机物对土壤Cd、Pb有效性的影响

在Cd、Pb污染土壤中,通过生物盆栽试验,研究了2种不同填埋年龄的垃圾渗滤液溶解性有机物(DOM)对黑麦草生长的影响及其对重金属Cd、Pb吸收的影响.鲜样、水阁样分别为填埋年龄0和12年的垃圾渗滤液.结果表明,垃圾渗滤液DOM施入土壤,残留在土壤中的DOM平均浓度为对照的1.39倍(鲜样)和1.47倍(水阁样).2种垃圾渗滤液DOM处理的土壤水溶态Cd、Pb和交换态Cd、Pb均在前期呈波动变化,到后期则上升.在Cd污染土壤中,鲜样和水阁样垃圾渗滤液DOM处理土壤水溶态Cd、交换态Cd分别高出对照37.44%、4.81%,48.97%、14.94%;在Pb污染土壤中,鲜样和水阁样垃圾渗滤液DOM处理土壤水溶态Pb、交换态Pb分别高出对照8.56%、7.22%,18.99%、11.47%.鲜样和水阁样垃圾渗滤液DOM处理黑麦草总Cd浓度分别高于对照19.59%和104.4%,总Pb浓度分别高36.03%和44.66%;但两处理的黑麦草总生物量下降14.03%～52.24%.因此,垃圾渗滤液DOM进入污染土壤后,有利于土壤重金属生物有效性的提高和植物体内重金属的累积,却抑制植物的生长, 尤以填埋年龄长的垃圾渗滤液DOM影响更大.     

拉布拉多犬的母性行为水平对幼犬胆量的影响

母性行为是动物以维持幼崽的生存及生理健康为主要目的的一种基本行为,母性行为作为重要的早期经历对动物的个体发展有深远影响。动物的行为在时间和环境中具有一致性,多个行为特征的一致性加权被称为气质特征,气质特征的差异是犬(Canis lupus familiaris)能否顺利通过培训成为导盲犬的决定性因素。其中,胆量是决定导盲犬培训成功与否的重要气质特征。本研究以中国导盲犬大连培训基地的拉布拉多种犬及幼犬为研究对象,探究母性行为水平对幼犬胆量的影响。本研究通过视频观察记录拉布拉多犬哺乳期前21 d的母性行为变量时长,对在哺乳区内、身体接触、哺乳和舔舐幼犬4项变量进行主成分分析后将7只实验犬分为母性行为高水平与低水平两组。对两组犬生产的共54只幼犬于6 ~ 8周龄时进行幼犬胆量行为测试,根据胆量行为测试的评分标准对幼犬的行为表现进行评分,统计分析母性行为高水平组与低水平组其幼犬的胆量是否存在差异。本研究结果表明,母性行为低水平组的幼犬在胆量测试中面对陌生环境、突然出现的响声刺激、突然打开的雨伞刺激以及陌生人的游戏邀请时均表现出更大的胆量。在被动测试中,母性行为低水平组幼犬的探索潜伏时长显著短于母性行为高水平组幼犬(P < 0.05),探索范围显著大于母性行为高水平组幼犬(P < 0.05),紧张程度极显著低于母性行为高水平组幼犬(P < 0.01);在金属响声测试中,母性行为低水平组幼犬的惊吓反应(P < 0.01)和紧张程度(P < 0.01)均极显著低于母性行为高水平组幼犬;在雨伞测试中,母性行为低水平组幼犬的紧张程度显著低于母性行为高水平组幼犬(P < 0.05);在玩具测试中,母性行为低水平组幼犬的玩耍兴趣显著高于母性行为高水平组幼犬(P < 0.05),紧张程度显著低于母性行为高水平组幼犬(P < 0.05);在斜坡隧道测试中,母性行为低水平组幼犬的紧张程度显著低于母性行为高水平组幼犬(P < 0.05),通过斜坡的用时短于母性行为高水平组幼犬,但经统计检验无显著差异(P > 0.05)。本研究的结论为低母性行为水平带给幼犬强度适当的早期生活压力,使幼犬面对新环境刺激时表现出更好的适应能力和较大的胆量。本研究为工作犬种犬的筛选提出新的建议：母性行为水平低的种犬对幼犬胆量的发展有更好的影响。     

茉莉酸类与植物地下贮藏器官的形成

茉莉酸类化合物(茉莉酸及其衍生物)可能参与了马铃薯、薯蓣、菊芋的块茎,甘薯的块根以及洋葱、大蒜的鳞茎形成。JA及MeJA均可诱导离体条件下马铃薯块茎的形成和马铃薯髓部细胞的膨大。JA诱导细胞膨大是由于蔗糖积累导致渗透压增加以及细胞壁结构变化,从而使其伸展性增加,纤维素的合成起了重要作用,细胞骨架也是JA诱导细胞膨大所必需的。但迄今为止,尚未确定块茎形成的直接诱导物。     

Formation of cellobiose lipids by growing and resting cells of Ustilago maydis

Summary Utilizing coconut oilUstilago maydis ATCC 14826 synthesizes cellobiose lipids under N-limitation conditions and as resting cells, which gave the highest specific biosurfactant production (0.79 g/g substrate). C6-, C12-, C14-, and 15, 16-dihydroxy-C16-fatty acids are the main components of the lipophilic moiety of these glycolipids.     

褐飞虱对抗性水稻品种Mudgo个体致害性指标

在28±1℃下,观测了褐飞虱Nilaparvata lugens羽化24?h内短翅型雌成虫在敏感水稻品种TN1及抗性品种Mudgo上的寿命及体重增量。结果表明,取食抗性品种时,试虫的平均增重与寿命之间表现出明显的正相关。寿命在7天内的个体,存活期间平均体重增量为负值,而存活7天以上的个体则平均增重明显。进一步研究了初羽化的褐飞虱长翅型雌成虫在TN1及Mudgo上取食第1～4天的体重增量、寿命及产卵量,结果发现试虫在Mudgo上的这3个生物学参数之间存在明显正相关。其中,寿命及体重增量较好地反映出害虫个体对抗性品种的致害能力,可作为个体致害性指标。根据研究结果,提出将羽化后在Mudgo上存活7天以上或最初4天内体重增量大于0.1mg的雌成虫定为能够致害该抗性品种的个体。     

Expanding the genetic code of Drosophila melanogaster

Genetic code expansion for unnatural amino acid mutagenesis has, until recently, been limited to cell culture. We demonstrate the site-specific incorporation of unnatural amino acids into proteins in Drosophila melanogaster at different developmental stages, in specific tissues and in a subset of cells within a tissue. This approach provides a foundation for probing and controlling processes in this established metazoan model organism with a new level of molecular precision.     

Maximizing antibody production in a targeted integration host by optimization of subunit gene dosage and position

Historically, therapeutic protein production in Chinese hamster ovary (CHO) cells has been accomplished by random integration (RI) of expression plasmids into the host cell genome. More recently, the development of targeted integration (TI) host cells has allowed for recombination of plasmid DNA into a predetermined genomic locus, eliminating one contributor to clone-to-clone variability. In this study, a TI host capable of simultaneously integrating two plasmids at the same genomic site was used to assess the effect of antibody heavy chain and light chain gene dosage on antibody productivity. Our results showed that increasing antibody gene copy number can increase specific productivity, but with diminishing returns as more antibody genes are added to the same TI locus. Random integration of additional antibody DNA copies in to a targeted integration cell line showed a further increase in specific productivity, suggesting that targeting additional genomic sites for gene integration may be beneficial. Additionally, the position of antibody genes in the two plasmids was observed to have a strong effect on antibody expression level. These findings shed light on vector design to maximize production of conventional antibodies or tune expression for proper assembly of complex or bispecific antibodies in a TI system.