送巧克力給男同事是「禮貌」？日本女性逐漸對「義理巧克力」說不

比如爱因斯坦，送巧克力給从广义相对论到狭义相对论，从量子力学到统计物理，在物理学的众多分支领域中，他都做出了开拓性贡献。

他强调，男同事禮学生会员从与评审委员互动过程中，能进一步发现自己和被发现。貌日本女性王绶琯称他们为科学家志愿者民间探索小分队。

王绶琯曾长期主持我国天文学的总体发展，逐漸對義理为天文事业奋斗七十年，为中国现代天文学的发展做出了巨大贡献。巧克力說爱因斯坦26岁发表狭义相对论。他们中还有的成长为高性能集成电路芯片设计领域知名专家，送巧克力給在国际学术界和工业界有一定影响力。男同事禮海森堡25岁提出测不准原理。同时，貌日本女性他也多次强调，俱乐部的科研实践活动，在执行中应严格排除应赛教育的影响，当然也并不干预学校将自己学生的科研成果参加正规的赛事。

王思远还问过黄力一个问题，逐漸對義理即21世纪生物学突破口应该在什么方向？ 黄老师认为，逐漸對義理21世纪应该是生物学和其他相近学科剧烈交叉的时代，物理学和生物学的交叉能带来更大的突破。各国综合国力的竞争，巧克力說归根结底是人才的竞争。看来您也没有关注到Helen Wise博士的综述论文，送巧克力給 G蛋白偶联受体的高度截短的剪接变体所起的作用。

（Liang MN and Garrison JC. The epidermal growth factor receptor is coupled to a pertussis toxin-sensitive guanine nucleotide regulatory protein in rat hepatocytes. J. Biol. Chem. 1991; 266(20):1342-9.） 2. CD47是一个5 次跨膜的膜蛋白，男同事禮研究表明，男同事禮CD47也能够结合并激活G蛋白及其下游信号。这个变体仍然能在细胞膜上表达，貌日本女性并保留了结合配体并激活Gq和Gs的功能。逐漸對義理学术争鸣在科学发展过程中具有举足轻重的作用。综述类引用：巧克力說27次，研究论文引用：57次。

目前已确认的人类GPCR有1265个，单个细胞类型通常表达一百种以上的GPCR，这些信号受体通过激活细胞中的各种G蛋白，影响着目前已知的人类生理病理的所有方面。我全力支持在中国各个层面将学生和院士的科研不当行为斩草除根。

该变体显示与野生型受体不同的细胞/组织表达谱，仍能结合配体并行使部分受体功能。（Theodore WK and Donald ME. Bacteriorhodopsin Can Be Refolded from Two Independently Stable Transmembrane Helices and the Complementary Five-Helix Fragment. Biochemistry. 1992; 31:6144-51.） 2. G蛋白偶联受体mGluR1需要形成二聚体来激活G蛋白信号通路。有趣的是，这个研究表明，缺失第1和第2. 跨膜区不影响这种二聚体的形成。这个五次跨膜的GHS受体可以与神经降压素NTS1受体形成异源受体二聚物，产生新的生理作用，这一发现可能为抑制非小细胞肺癌细胞生长，提供了全新的药物靶标。

此外，受质疑论文的3位第一作者（通讯作者为裴钢院士）向科学网提供了和这篇论文相关的综述材料。这个研究发现，SST5受体基因可以产生只有5个跨膜区的仍然具备功能的天然变体。（Belenikin MS, Costantino G, Palyulin VA, Pellicciari R, Zefirov NS. Molecular modeling of the mGluR1 metabotropic glutamate receptor transmembrane domain and construction of the model of its dimer. Dokl. Biochem. Biophys. 2003; 393:341-5.） 3. 编码GnRH-II受体的基因除表达野生型7次跨膜受体外，也可以产生5次跨膜的天然截短变体。除此之外，其他非7次跨膜结构的膜受体对激活G蛋白信号的贡献也不可忽视，这些受体可能对GPCR的功能起到补充和调节作用，理解其中的分子机制有可能为我们的药物设计另辟蹊径，提供崭新的思路。

为了支持裴钢博士的科学科研成果，请您参考近几年我在麻省理工学院的研究成果工作。来源：科学网微信公号 发布时间：2021/1/22 16:59:07 选择字号：小 中 大 张曙光VS饶毅：关于裴钢被质疑论文的争鸣 编 者 按 1月22日，美国麻省理工学院分子结构实验室（Laboratory of Molecular Architecture）首席研究员（Head）张曙光向科学网提供了一份当天致饶毅教授的信件，就后者21日晚在其个人公号饶议科学上正式举报林-裴(1999)论文涉嫌学术不端一文发表看法。

这些研究显示，特定GPCR家族成员具有不同于普适规律的个性，揭示了细胞调节G蛋白信号的新颖方式，有助于我们理解复杂的细胞生理病理的分子机制，制定与之对应的特异的干预办法，为药物研发等提示新的思路。对照7次跨膜的野生型受体，这些跨膜区缺失的变体表现出相似的表达水平和功能。

相应的，至少有50％的上市药物靶标是GPCR家族成员。我认为您的指责完全没有道理，您必须真诚地向裴钢博士及其同事道歉。令人惊讶的是，您竟然可以在完全不阅读文献的情况下提出了如此严重的指控。（Durn-Prado M, Gahete MD, Martnez-Fuentes AJ, Luque RM, Quintero A, Webb SM, Benito-Lpez P, Leal A, Schulz S, Gracia-Navarro F, Malagn MM, Castao JP. Identification and characterization of two novel truncated but functional isoforms of the somatostatin receptor subtype 5 differentially present in pituitary tumors. J. Clin. Endocrinol Metab. 2009; 94(7):2634-43. ） 7. Castao研究组的后续研究发现，SST5受体基因还能够产生只有4，2，或1个跨膜区的天然截短变体。研究发现PKR2基因转录产物存在天然剪切变体，产生一个缺失第1-3跨膜区的截短变体。（Neill JD, Musgrove LC, Duck LW. Newly recognized GnRH receptors: function and relative role. Trends Endocrinol Metab. 2004; 15(8):383-92.） 4. 二型神经降压素NTS2 受体是一种G蛋白偶联受体，其编码基因能够产生5次跨膜的天然变体。

您在不熟悉相关科学文献的情况下提出的指控，在科学和伦理上都是完全不负责任的。我们的论文不仅证实了凌堃等人1999年报道在PNAS 上的Five-transmembrane domains appear sufficient for a G protein-coupled receptor: Functional five-transmembrane domain chemokine receptors工作中报告的结果，也明确地表明，只有2个或3个跨膜片段的CXCR4和CCR5突变体能够显示出配体结合活性、能够定位到细胞质膜上、并能够进行细胞信号转导。

在我们的研究发表之后，更多类似的特例被陆续发现，包括一些GPCR经过转录剪切而产生的天然跨膜区缺失变体（包括5次跨膜及其他类型的跨膜区缺失），为研究GPCR结构功能而人为制作的跨膜区缺失变体， 以及一些非7次跨膜的其他种类的膜受体，这些非典型的GPCR受体仍能介导G蛋白下游信号。为此我们需要认真地将每种GPCR视为一个独特的实例，具体到不同细胞、组织、代谢及时空的维度上，仔细评估它们对于细胞生理病理进程及药理反应的意义。

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您鲁莽的指控，对于被指控者，尤其是年轻科学家的科学声誉和科研生涯造成极大损害。这些结果表明，各个跨膜区的重要性在不同的GPCR中可以有很大的差异，5次跨膜或其他少于7次跨膜的GPCR可以通过形成同源或异源多聚体的方式，至少部分行使结合配体并激活下游G蛋白信号的功能。1. 张曙光致饶毅信件全文 饶毅博士： 我对您针对裴钢博士及其同事1999年在PNAS上发表的论文提出指控却没有认真阅读相关科学文献感到非常震惊。对GPCR截短变体的研究，特别是对其在特定细胞或组织的生理病理过程的研究，有可能补充常规GPCR受体的研究，为相关人类疾病提供新的药物靶标。

（Bokaei PB, Ma XZ, Byczynski B, Keller J, Sakac D, Fahim S, Branch DR. Identification and characterization of five-transmembrane isoforms of human vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors. Genomics 2006; 88:791-800.） 6. 人类生长抑素SST5受体是一种G蛋白偶联受体。该变体显示与野生型NTS2受体一样的组织/器官表达谱，并通过形成同源或异源二聚体和多聚体完成受体功能。

如其他媒体、网站或个人从本网站转载使用，须保留本网站注明的来源，并自负版权等法律责任。（Parnell SC, Magenheimer BS, Maser RL, Zien CA, Frischauf AM, Calvet JP. J Biol Chem. 2002; 277(22):19566-72.） 4. Cook研究组的研究显示，Toll-like receptor 4作为一个单次跨膜的受体，也能激活G蛋白信号通路。

其中自引：8次，他引：76次。国外医学(分子生物学分册), 2001年01期。

我们的研究结果已经以Non-full-length Water-Soluble CXCR4QTY and CCR5QTY Chemokine Receptors: Implication for Overlooked Truncated but Functional Membrane Receptors 为题，2020年报道发表在Cell子刊iScience(Cell Press)上。作为全球华人科学家社区，科学网特发布各方观点，希望能促进彼此间的理性对话，弘扬好追求真理、严谨治学的求实精神古代经典名方获认同 特别值得一提的是，中医药在新冠疫情中发挥了重要作用，更为其产业化发展提供了良好契机。2020年，国家药品监督管理局共受理国产1类创新药注册申请828个，最终获批上市的1类新药14个。

随后，各地药品监督管理局加快审批医院制剂。按药品类型统计，化学药574个、生物制品254个。

突破性治疗公示专栏的首次公示，标志着这一特殊审评通道正式在我国启动。作者：刘昌孝 来源：中国科学报 发布时间：2021/1/22 10:33:08 选择字号：小 中 大 刘昌孝院士：中国生物医药步入快车道 新冠疫情是2020年全球最值得关注的公共卫生事件，它也必将载入人类史册。

诸多防控项目获得国家、省级防治新冠肺炎科技攻关专项应急立项。新冠病毒的主蛋白酶在病毒生活周期中有关键调节作用，是一个备受瞩目的药物靶点。