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杂质产生的假阳性会导致化学感觉研究中受体的功能特征分析出现错误。

False positives from impurities result in incorrect functional characterization of receptors in chemosensory studies.

机构信息

Department of Plant Protection Biology, Division of Chemical Ecology, Swedish University of Agricultural Sciences, Alnarp, Sweden; Sørengkaia 115, 0194 Oslo, Norway.

Zoology Department, Plant Protection Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary.

出版信息

Prog Neurobiol. 2019 Oct;181:101661. doi: 10.1016/j.pneurobio.2019.101661. Epub 2019 Jul 13.

DOI:10.1016/j.pneurobio.2019.101661
PMID:31310789
Abstract

The discovery of chemoreceptors and technological advances have greatly increased our understanding of chemosensory mechanisms. However, some of this rapid progress may have been severely compromised by insufficient attention given to the possible effects of impurities in the chemical standards used in identifying ligands for target receptors. Here, we show that even trace amounts of impurities in test stimuli can completely obscure true ligand-receptor relationships. Responses to impurities may go unrecognized because of two main factors. First, the sensitivity of receptors to ligands may be greater than that of the instruments used to check sample purity. Second, the concentrations of impurities actually reaching the chemoreceptor during experiments may be orders of magnitude higher than that of the putative stimulus, due to large differences in vapour pressure between the impurities and the putative stimulus. Errors caused by impurities are not limited to receptor-ligand studies, but can also affect related areas of chemosensory research, such as neural processing, downstream behaviours, and "in-silico" bioinformatics predictions of response profiles. The purity of standards is always implied but must be checked rigorously to prevent skewed or invalid results or conclusions, such as we exemplify here for Drosophila melanogaster and its olfactory receptor DmOr7a.

摘要

化学感受器的发现和技术进步极大地提高了我们对化学感觉机制的理解。然而,由于对用于鉴定靶受体配体的化学标准品中杂质可能产生的影响重视不够,这种快速进展可能受到了严重影响。在这里,我们表明,即使测试刺激物中痕量的杂质也可能完全掩盖真正的配体-受体关系。由于两个主要因素,对杂质的反应可能未被识别。首先,受体对配体的敏感性可能高于用于检查样品纯度的仪器。其次,由于杂质和假定刺激物之间的蒸气压差异很大,在实验过程中实际到达化学感受器的杂质浓度可能比假定刺激物高出几个数量级。杂质引起的误差不仅限于受体-配体研究,还会影响化学感觉研究的相关领域,例如神经处理、下游行为以及对反应谱的“计算机”生物信息学预测。标准品的纯度总是隐含的,但必须严格检查,以防止出现偏差或无效的结果或结论,例如我们在这里以果蝇及其嗅觉受体 DmOr7a 为例进行说明。

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