When examining the medical doctrines of previous empires, they reveal the influence of religion, societal attitudes, and the historical context that influenced the scholars that penned them. The advancements during the Islamic Golden age can be seen in the field of medicine, which had the Greco-Roman medical corpus as their foundation and the source of the theory of the four humors and anatomical beliefs. This paper will analyze the effect of cultural, societal, and historical influences on the medical doctrines of Muslim medieval physicians in the Golden Age and the works of the Roman physician Galen, and demonstrate how these effects result in similarities and differences in medical practice and the understanding of disease and anatomy. Due to translation efforts that were supported by religious views on the accumulation of knowledge and the efforts of the Abbasid empire, resultant acceptance of the theory of the four humors and anatomical doctrines is observed in the treatment and perception of disease, which would consist of this paper's focus on surgery, diet therapy and associations with nature. However, with further analysis of the extent of this acceptance and the findings in the Islamic medical doctrines, the differences in experimental methods, religious interpretations, and cultural attitudes shows a deviation from the Galenic tradition, with the second set of the paper's focus being human dissection, cause of disease, and experimentation. The purpose of this research is to demonstrate the impact of religion, societal attitudes, culture and the accepted paradigm on the practice of medicine and the study of anatomy, and what would cause a challenge against the legacy of Galen.
The membrane proximal region (MPR, residues 649–683) and transmembrane domain (TMD, residues 684–705) of the gp41 subunit of HIV-1’s envelope protein are highly conserved and are important in viral mucosal transmission, virus attachment and membrane fusion with target cells. Several structures of the trimeric membrane proximal external region (residues 662–683) of MPR have been reported at the atomic level; however, the atomic structure of the TMD still remains unknown. To elucidate the structure of both MPR and TMD, we expressed the region spanning both domains, MPR-TM (residues 649–705), in Escherichia coli as a fusion protein with maltose binding protein (MBP). MPR-TM was initially fused to the C-terminus of MBP via a 42 aa-long linker containing a TEV protease recognition site (MBP-linker-MPR-TM).
Biophysical characterization indicated that the purified MBP-linker-MPR-TM protein was a monodisperse and stable candidate for crystallization. However, crystals of the MBP-linker-MPR-TM protein could not be obtained in extensive crystallization screens. It is possible that the 42 residue-long linker between MBP and MPR-TM was interfering with crystal formation. To test this hypothesis, the 42 residue-long linker was replaced with three alanine residues. The fusion protein, MBP-AAA-MPR-TM, was similarly purified and characterized. Significantly, both the MBP-linker-MPR-TM and MBP-AAA-MPR-TM proteins strongly interacted with broadly neutralizing monoclonal antibodies 2F5 and 4E10. With epitopes accessible to the broadly neutralizing antibodies, these MBP/MPR-TM recombinant proteins may be in immunologically relevant conformations that mimic a pre-hairpin intermediate of gp41.