GAPDH is a conserved enzyme that binds diverse proteins, such as Siah during apoptotic nuclear translocation. There is one somatic GAPDH gene, but over 60 pseudogenes, the expression of which is nebulous. A single nuc...GAPDH is a conserved enzyme that binds diverse proteins, such as Siah during apoptotic nuclear translocation. There is one somatic GAPDH gene, but over 60 pseudogenes, the expression of which is nebulous. A single nucleotide polymorphism (SNP) in the GAPDHP44 pseudogene exhibits a beneficial allele in AD. The objective of this study was to examine the P44 gene and to propose a mechanism for the putative protein and its impact on AD. We examined the sequences in the putative coding region of the human GAPDHP44 gene and the upstream genetic elements usinga bioinformatics approach. We compared the amino acid sequences of the putative gene product with that of the parent GAPDH protein. There is a TATA box 24 nt upstream from, and a Kozak sequence at, putative transcription and translation start sites, respecttively. The upstream region also has sequences (7 - 16 nt) paralogous to those in parent gene introns;one shows homology to a known enhancer element. The resulting protein would contain 139 aa due to a stop codon, roughly the same size as the dinucleotide domain (151 aa) of the parent protein. The SNP is in a region (residues 80 - 120) that binds to the protein GOSPEL. We propose that the beneficial SNP may cause a glutamine to glutamate substitution. NMDA-stmulated neurons undergo GAPDH nitrosylation, Siah translocation, but can be rescued by GOSPEL binding to GAPDH. Our model suggests that the putative P44 protein may regulate GAPDH-GO-SPEL interaction and the beneficial SNPmay ameliorate AD.展开更多
一、问题缘起1972年马库尔德(Friedrich-Wilhelm Marquardt,1928-2002)出版了他的著作《神学与社会主义:以卡尔·巴特为例》(Theologie und Sozialismus:Das Beispiel Karl Barths)。他直言:"早在当今的基督徒与马克思主义者...一、问题缘起1972年马库尔德(Friedrich-Wilhelm Marquardt,1928-2002)出版了他的著作《神学与社会主义:以卡尔·巴特为例》(Theologie und Sozialismus:Das Beispiel Karl Barths)。他直言:"早在当今的基督徒与马克思主义者对话之前,巴特在他的神学中已发展出了社会主义内容(sozialistischen Gehalt)。"(1)由此,德语神学界掀起了一场持久不休的激烈争论,并因此而分裂为左翼和右翼巴特神学阵营。展开更多
一个新的起点此文旨在通过被新约学者们称为"第五福音书"的《多马福音》(The Gopsel of Thomas)拓展我们对基督教起源的理解视角。正如学者们所知,在这部福音书中,大约有一半的内容都与对观福音书相吻合,然而它却使用了一种...一个新的起点此文旨在通过被新约学者们称为"第五福音书"的《多马福音》(The Gopsel of Thomas)拓展我们对基督教起源的理解视角。正如学者们所知,在这部福音书中,大约有一半的内容都与对观福音书相吻合,然而它却使用了一种独特的方式——语录汇编——来呈现这些大体相似的内容;由此,它被理解为是一种迥然不同的神学类型:智慧神学。这是一部独特的福音书,一部智慧福音,在这部福音书中,耶稣的话语(logoi)处于核心地位。展开更多
文摘GAPDH is a conserved enzyme that binds diverse proteins, such as Siah during apoptotic nuclear translocation. There is one somatic GAPDH gene, but over 60 pseudogenes, the expression of which is nebulous. A single nucleotide polymorphism (SNP) in the GAPDHP44 pseudogene exhibits a beneficial allele in AD. The objective of this study was to examine the P44 gene and to propose a mechanism for the putative protein and its impact on AD. We examined the sequences in the putative coding region of the human GAPDHP44 gene and the upstream genetic elements usinga bioinformatics approach. We compared the amino acid sequences of the putative gene product with that of the parent GAPDH protein. There is a TATA box 24 nt upstream from, and a Kozak sequence at, putative transcription and translation start sites, respecttively. The upstream region also has sequences (7 - 16 nt) paralogous to those in parent gene introns;one shows homology to a known enhancer element. The resulting protein would contain 139 aa due to a stop codon, roughly the same size as the dinucleotide domain (151 aa) of the parent protein. The SNP is in a region (residues 80 - 120) that binds to the protein GOSPEL. We propose that the beneficial SNP may cause a glutamine to glutamate substitution. NMDA-stmulated neurons undergo GAPDH nitrosylation, Siah translocation, but can be rescued by GOSPEL binding to GAPDH. Our model suggests that the putative P44 protein may regulate GAPDH-GO-SPEL interaction and the beneficial SNPmay ameliorate AD.
文摘一、问题缘起1972年马库尔德(Friedrich-Wilhelm Marquardt,1928-2002)出版了他的著作《神学与社会主义:以卡尔·巴特为例》(Theologie und Sozialismus:Das Beispiel Karl Barths)。他直言:"早在当今的基督徒与马克思主义者对话之前,巴特在他的神学中已发展出了社会主义内容(sozialistischen Gehalt)。"(1)由此,德语神学界掀起了一场持久不休的激烈争论,并因此而分裂为左翼和右翼巴特神学阵营。
文摘一个新的起点此文旨在通过被新约学者们称为"第五福音书"的《多马福音》(The Gopsel of Thomas)拓展我们对基督教起源的理解视角。正如学者们所知,在这部福音书中,大约有一半的内容都与对观福音书相吻合,然而它却使用了一种独特的方式——语录汇编——来呈现这些大体相似的内容;由此,它被理解为是一种迥然不同的神学类型:智慧神学。这是一部独特的福音书,一部智慧福音,在这部福音书中,耶稣的话语(logoi)处于核心地位。
