The research aims to explore the evolutionary adaptability of enzymes and the impact of temperature on protein evolution pathways, using M. tuberculosis β-lactamase BlaC as the object of study.... Show moreThe research aims to explore the evolutionary adaptability of enzymes and the impact of temperature on protein evolution pathways, using M. tuberculosis β-lactamase BlaC as the object of study. Enzymes inherently embody a delicate balance between activity and stability, and the acquisition of new enzymatic functions is often accompanied by trade-offs, such as decreased stability or reduction of the original activity. Probing evolutionary adaptability of BlaC with laboratory evolution in combination with structural characterization can provide information about the mechanisms of rapid adaptations observed for β-lactamases in the clinic. The role of temperature as a conventional selection pressure in such evolutionary adaptation is unclear. The cooperative nature of enzyme unfolding over a narrow temperature trajectory raises the question whether evolution at temperatures well below the melting point is influenced by temperature. The approach used in this work to answer these questions is by simulating evolution under different selection pressures and characterize the variant enzymes in terms of activity, structure, dynamics and melting temperature. The research makes clear how enzyme kinetics and dynamics vary with different selection pressures and maps the evolutionary path that enzymes may take. The underlying structural mechanisms are established to provide a rationale for the observed effects. Show less
Ever since the seven so-called earliest Chinese Christian manuscripts were removed from Dunhuang Cave 17 in 1900 and published by the first generation of scholars, they were quickly recognized... Show moreEver since the seven so-called earliest Chinese Christian manuscripts were removed from Dunhuang Cave 17 in 1900 and published by the first generation of scholars, they were quickly recognized as sources used by the Tang church, an offshoot of the Church of the East that entered China in 635 and allegedly disappeared after 845. This empirical, technical and philological work, however, finds: The putative earliest manuscripts made in the 640s, The Messiah Sutra and On One God, might be the latest sources that were created between 800-1010s. The only two dated sources, Kojima Manuscripts A and B, are modern forgeries. Only two manuscripts, Mysterious Bliss Sutra and Sutra of Origins of Daqin Jingjiao, are actual Tang documents that may be made between 745 and 787. Manuscript P.3847 is the work of post-Tang Christians. All the findings, as a whole, give us food for thought, encouraging us to rethink the traditional historiography of Christianity in China before 1200. It compels us to draw a picture of a local Dunhuang Christian community. It also prompts us to alter our current thinking about the institution known as the Tang church. Moreover, it challenges the present consensus that Christianity was extinguished after 845. Show less