科学家已经勾勒出如此一副画面，将来在家自制吗啡会和自制啤酒一样简单。 在家做啤酒，依靠的是酵母将糖转化成酒精的能力。科学家通过将植物 DNA 通过基因工程嫁接给酵母，让酵母具备一步步将糖转化为吗啡所需系列较复杂化学反应的能力。 其实将微生物用于制药并不是什么新鲜事情，像糖尿病人用的胰岛素，就是通过转基因改造的细菌生产出来的。 吗啡用于镇痛，要通过罂粟获取；若能通过微生物完成这一过程，无疑将更加简单，廉价。 虽然初衷是用于制药，但这无疑将引起关于自制毒品的忧虑：在原则上，只要能够得到这类酵母菌株，具备基本的发酵技巧，就可以像在家自制啤酒一样 DIY 毒品出来，这无疑是一种很可怕的事情。 立法端正科研行为，管控好这类基因改造的微生物，当未雨绸缪。 http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.1816.html An enzyme-coupledbiosensor enables (S)-reticuline production in yeast from glucose Benzylisoquinolinealkaloids (BIAs) are a diverse family of plant-specialized metabolites thatinclude the pharmaceuticals codeine and morphine and their derivatives.Microbial synthesis of BIAs holds promise as an alternative to traditionalcrop-based manufacturing. Here we demonstrate the production of the key BIAintermediate (S)-reticuline from glucose in Saccharomyces cerevisiae. To aid inthis effort, we developed an enzyme-coupled biosensor for the upstreamintermediate L-3,4-dihydroxyphenylalanine (L-DOPA). Using this sensor, weidentified an active tyrosine hydroxylase and improved its L-DOPA yields by 2.8-foldvia PCR mutagenesis. Coexpression of DOPA decarboxylase enabled what is to ourknowledge the first demonstration of dopamine production from glucose in yeast,with a 7.4-fold improvement in titer obtained for our best mutant enzyme. Weextended this pathway to fully reconstitute the seven-enzyme pathway fromL-tyrosine to (S)-reticuline. Future work to improve titers and connect thesesteps with downstream pathway branches, already demonstrated in S. cerevisiae,will enable low-cost production of many high-value BIAs. 群晓科苑 qbioscience.com
在室温下，利用太赫兹时域光谱技术获得了一系列毒品（吗啡及其盐酸盐，可卡因，可待因，哌替啶，罂粟碱和蒂巴因）的低频振动光谱。利用密度泛函理论对吗啡进行结构优化和低频振动计算。结合理论计算，吗啡在太赫兹波段的吸收归结为分子间/分子内的集体或晶格振动模式。结果表明，不同的毒品在太赫兹波段呈现不同的吸收特征，因此可以利用该技术对毒品进行检测。 Nuclear Science and Techniques 21 (2010) 209–213 Cited by： 1， Investigation of solid-state reaction by terahertz time-domain spectroscopy Nuclear Science and Techniques 22(2011) 139–143 2, SOLID-STATE REACTION BETWEEN P-BENZOQUINONE AND 4,4 '-BIPHENOL: A THz TIME-DOMAIN SPECTROSCOPIC STUDY JOURNAL OF APPLIED SPECTROSCOPY78(2011) 318-325
http://www.sciencenet.cn/htmlpaper/20091191532467707705.shtm?id=7705 吗啡镇痛机制研究获新进展 图1 吗啡显著降低神经元对伤害性刺激的反应 图2 吗啡大大削弱了各脑区神经元对伤害性刺激的分辨能力 吗啡及其他阿片类激动剂因其强大的镇痛作用被广泛应用于临床上对疼痛的治疗。然而，人类对于阿片类药物在脊髓水平之上的镇痛机制的认识却很有限。 中科院心理所心理健康院重点实验室罗非研究员、王锦琰副研究员及其团队利用清醒动物神经细胞群单位放电多通道同步记录技术，在大鼠的初级躯体感觉皮层(SI)，丘脑腹后外侧核(VPL)，前扣带皮层(ACC)以及丘脑背内侧核(MD)埋置电极，研究吗啡在疼痛的内外侧通路对伤害性感觉加工的调节作用。其中，SI和VPL位于疼痛加工的外侧通路，处理疼痛的感觉信息，而ACC和MD位于疼痛加工的内侧通路，处理疼痛的情绪信息。结果表明，大鼠腹腔注射5mg/kg的吗啡能够显著降低伤害性热辐射刺激所引发的四个脑区神经元活动的改变，包括降低神经元对热辐射刺激的反应幅度、反应比例、反应持续时间，以及削弱皮层和丘脑神经元群对伤害性刺激和非伤害性刺激的分辨能力。另外，吗啡还能够抑制由疼痛引起的内、外侧通路之间以及皮层-丘脑之间的信息流动，该效应能够被阿片受体拮抗剂纳洛酮所阻断。上述研究结果表明，吗啡通过抑制疼痛的情绪和感觉维度起到镇痛作用，进而在皮层和丘脑水平阐明了吗啡的镇痛机制。该研究对于吗啡镇痛机制的基础研究起到了推动作用，为临床治疗提供了有力的理论依据。 此文章已发表于《分子疼痛》（ Molecular Pain ）。（来源：中科院心理研究所） 更多阅读 《分子疼痛》发表论文摘要（英文） http://www.molecularpain.com/content/5/1/60/abstract Morphine modulation of pain processing in medial and lateral pain pathways Jin-Yan Wang * 1 , Jin Huang * 2 , Jing-Yu Chang 3 , Donald J Woodward 3 and Fei Luo 1 1 Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Science, Beijing, China 2 Neuroscience Research Institute, Peking University, Beijing, China 3 Neuroscience Research Institute of North Carolina, Winston-Salem, NC, USA author email corresponding author email * Contributed equally Molecular Pain 2009, 5 : 60 doi:10.1186/1744-8069-5-60 Published: 13October2009 Abstract Background Despite the wide-spread use of morphine and related opioid agonists in clinic and their powerful analgesic effects, our understanding of the neural mechanisms underlying opioid analgesia at supraspinal levels is quite limited. The present study was designed to investigate the modulative effect of morphine on nociceptive processing in the medial and lateral pain pathways using a multiple single-unit recording technique. Pain evoked neuronal activities were simultaneously recorded from the primary somatosensory cortex (SI), ventral posterolateral thalamus (VPL), anterior cingulate cortex (ACC), and medial dorsal thalamus (MD) with eight-wire microelectrode arrays in awake rats. Results The results showed that the noxious heat evoked responses of single neurons in all of the four areas were depressed after systemic injection of 5 mg/kg morphine. The depressive effects of morphine included (i) decreasing the neuronal response magnitude; (ii) reducing the fraction of responding neurons, and (iii) shortening the response duration. In addition, the capability of cortical and thalamic neural ensembles to discriminate noxious from innocuous stimuli was decreased by morphine within both pain pathways. Meanwhile, morphine suppressed the pain-evoked changes in the information flow from medial to lateral pathway and from cortex to thalamus. These effects were completely blocked by pre-treatment with the opiate receptor antagonist naloxone. Conclusion These results suggest that morphine exerts analgesic effects through suppressing both sensory and affective dimensions of pain. 相关文献信息分析 http://www.gopubmed.org/web/gopubmed/1?WEB01mbv78q8trrwxI4wI1I00f01000j10040001rl 检索策略 (morphine and analgesic effects) =Analgesics Rats 2,626 of 28,508 documents semantically analyzed Term: Rats Description: The common name for the genus Rattus. Synonyms: Laboratory Rats, Rattus, Rat, Rattus norvegicus, Laboratory Rat 1 2 3 Top Years Publications 1992 96 1991 93 1993 91 1982 90 1994 88 2005 87 2008 84 1989 83 1985 83 2007 81 1988 81 2000 80 2003 79 1998 78 1990 78 1983 77 1984 75 1978 75 1986 74 2004 72 1 2 3 1 2 3 Top Countries Publications USA 655 Japan 128 France 108 Canada 82 United Kingdom 73 Italy 73 China 57 Germany 49 Brazil 43 Sweden 34 Spain 33 Poland 32 Taiwan 31 Mexico 29 Iran 26 Australia 22 India 20 Hungary 20 Russia 19 Denmark 11 1 2 3 1 2 3 ... 17 Top Cities Publications Chicago 46 Paris 43 New York 39 Montreal 38 Tokyo 32 London 29 San Francisco 29 Beijing 27 Richmond 26 San Diego 24 Chapel Hill 24 Mexico City 23 Boston 22 Milan 21 Taipei 20 Baltimore 18 Kingston, Canada 17 Tehran 16 Lexington 15 Krakw 14 1 2 3 ... 17 1 2 3 ... 19 Top Journals Publications Eur J Pharmacol 230 Brain Res 168 J Pharmacol Exp Ther 155 Pharmacol Biochem Be 146 Pain 136 Life Sci 99 Psychopharmacology 91 Brit J Pharmacol 84 Neuropharmacology 60 Neurosci Lett 59 Anesthesiology 56 Anesth Analg 47 J Med Chem 44 Neuroscience 40 Arch Int Pharmacodyn Ther 39 Nippon Yakurigaku Zasshi 37 Arzneimittel-forsch 34 J Pharm Pharmacol 29 Jpn J Pharmacol 29 Pol J Pharmacol Pharm 27 1 2 3 ... 19 1 2 3 ... 268 Top Terms Publications Analgesics 2,626 Animals 2,622 Rats 2,622 Morphine 2,525 response to morphine 2,290 Analgesics, Opioid 1,290 Analgesia 932 Naloxone 814 Rats, Sprague-Dawley 782 Pharmaceutical Preparations 700 Dose-Response Relationship, Drug 699 Receptors, Opioid 684 Rats, Inbred Strains 675 Pain Measurement 641 Pain 597 Mice 505 Drug Tolerance 461 Reaction Time 441 Spinal Cord 438 opioid receptor activity 420 1 2 3 ... 268 1 2 3 ... 323 Top Authors Publications Bodnar R 39 Bhargava H 36 Pasternak G 30 Holtzman S 30 Yaksh T 25 Porreca F 21 Han J 21 Wiesenfeld-Hallin Z 21 Besson J 21 Xu X 20 Roques B 20 Kayser V 20 Guilbaud G 20 Mayer D 19 Fields H 18 Colpaert F 17 Dickenson A 16 Ferreira S 16 Fournie-Zaluski M 15 Malec D 15 1 2 3 ... 323
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