中国体制内

民间科学家团队

打破传统，挑战经典，

创”新时代“下做出了

一个重大的颠覆性发现：

第一个分泌型转录因子存在血浆中，

其前提是氧化还原敏感的跨膜糖蛋白分布于造血及多种实体组织内。

以其独特拓扑生物学折叠并锚定于细胞内质网，

在近膜外区域加工修饰而成熟之后释放入血；

成熟分子也可转运到细胞核发挥弱转录活性(或转录抑制性)

但是这里许许多多的开放性问题需要回答。

就此重大发现之初期工作提交多次基金申请，

但是

完完全全彻底地腰斩——这些原始创新的基金申请

即使被认为是“非经典”的应急基金申请也被枪杀得无影无踪。

请问中国体制内民间科学家如何继续开创性科学研究？

该文已经发表储存于冷泉港预印本数据库

https://www.biorxiv.org/content/early/2018/06/09/342428

为此，我们开辟该领域工作在生命医学科学界夺得了首发权。

去年就这个重大发现已经申请了中国发明专利保护，现仍处在公开阶段。

其全文已在投稿评审阶段。

对该文感兴趣的学者，

请下载已上传的全文。

Nrf1D_V1bioRxiv0.pdf

欢迎学术界朋友进行科学质疑与批判，

也展开国际间的真科实际合作。

该论文题目与摘要如下：

Nrf1D is the first candidate secretory transcription factor in the blood plasma,

with its precursor existing as a unique redox-sensitive transmembrane

CNC-bZIP protein in haemopoietic and somatic tissues

Jianxin Yuan^1,§, Hongxia Wang^1,§, Shaojun Li^1,§, Yuancai Xiang¹

Shaofan Hu¹, Meng Wang¹, Lu Qiu¹, and Yiguo Zhang*

¹Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.

^§Contributed equally to this work.

Abstract: Amongst multiple distinct isoforms, Nrf1D is synthesized from translation of an alternatively-spliced transcript of Nrf1 mRNA, with a naturally-occurring deletion of its stop codon-flanking 1466 nucleotides. This molecular event leads to the reading frameshift mutation, which results in a constitutive substitution of the intact Nrf1's C-terminal 72 amino acids (aa, covering the second half of the leucine zipper motif to C-terminal Neh3L domain) by an additional extended 80-aa stretch to generate a unique variant Nrf1D. The C-terminal extra 80-aa region of Nrf1D was identified to fold into a redox-sensitive transmembrane domain that enables it to be tightly integrated within the endoplasmic reticulum (ER) membranes. Notably, the salient feature of Nrf1D confers it to be distinguishable from prototypic Nrf1, such that Nrf1D is endowed with only a less ability than wild-type Nrf1 at mediating target gene expression. Further evidence has been presented revealing that both mRNA and protein levels of Nrf1D, along with Nrf1, were detected to varying extents in haemopoietic and somatic tissues. Surprisingly, we found the existence of Nrf1D-derived isoforms in the blood plasma, implying that it is a candidate secretory transcription factor, although its precursor acts as an integral transmembrane- bound CNC-bZIP protein that entails dynamic topologies, before being unleashed from the ER to enter the blood.

Key words: Nrf1, Nrf1D, secretory transcription factor, transmembrane, redox stress, alternative splicing

Running title: Nrf1D is the first candidate secretory transcription factor