Adaptive evolution of G-protein coupled receptor genes

The phylogeny and patterns of nucleotide substitutions in the visual pigment genes, adrenergic receptor genes, muscarinic receptor genes, and in the human mas oncogene were studied by comparing their DNA sequences. The evolutionary tree obtained shows that the visual pigment genes and mas oncogene form one cluster and that the receptor genes form another. In the evolution of rhodopsin genes, synonymous substitutions outnumber nonsynonymous substitutions. This is consistent with the neutral theory of molecular evolution. However, the early evolutionary stages of alpha- and beta-adrenergic and muscarinic receptors are notable for significantly more nonsynonymous substitutions than synonymous substitutions, suggesting the acquisition of novel functional adaptations. Variable rates of nonsynonymous changes in different domains of these proteins reveal DNA segments that might have been important in their functional adaptations.      

Failure to detect simian immunodeficiency virus infection in a large Cameroonian cohort with high non-human primate exposure

Hunting and butchering of wildlife in Central Africa are known risk factors for a variety of human diseases, including HIV/AIDS. Due to the high incidence of human exposure to body fluids of non-human primates, the significant prevalence of simian immunodeficiency virus (SIV) in non-human primates, and hunting/butchering associated cross-species transmission of other retroviruses in Central Africa, it is possible that SIV is actively transmitted to humans from primate species other than mangabeys, chimpanzees, and/or gorillas. We evaluated SIV transmission to humans by screening 2,436 individuals that hunt and butcher non-human primates, a population in which simian foamy virus and simian T-lymphotropic virus were previously detected. We identified 23 individuals with high seroreactivity to SIV. Nucleic acid sequences of SIV genes could not be detected, suggesting that SIV infection in humans could occur at a lower frequency than infections with other retroviruses, including simian foamy virus and simian T-lymphotropic virus. Additional studies on human populations at risk for non-human primate zoonosis are necessary to determine whether these results are due to viral/host characteristics or are indicative of low SIV prevalence in primate species consumed as bushmeat as compared to other retroviruses in Cameroon.     

Functional and structural insight into properdin control of complement alternative pathway amplification

Properdin (FP) is an essential positive regulator of the complement alternative pathway (AP) providing stabilization of the C3 and C5 convertases, but its oligomeric nature challenges structural analysis. We describe here a novel FP deficiency (E244K) caused by a single point mutation which results in a very low level of AP activity. Recombinant FP E244K is monomeric, fails to support bacteriolysis, and binds weakly to C3 products. We compare this to a monomeric unit excised from oligomeric FP, which is also dysfunctional in bacteriolysis but binds the AP proconvertase, C3 convertase, C3 products and partially stabilizes the convertase. The crystal structure of such a FP-convertase complex suggests that the major contact between FP and the AP convertase is mediated by a single FP thrombospondin repeat and a small region in C3b. Small angle X-ray scattering indicates that FP E244K is trapped in a compact conformation preventing its oligomerization. Our studies demonstrate an essential role of FP oligomerization in vivo while our monomers enable detailed structural insight paving the way for novel modulators of complement.     

A dye-binding induced conformational transition of poly-(methacrylic acid) by Auramine O in aqueous solutions. I. Experimental results

Binding of auramine O to poly-(methacrylic acid) (PMA) has been established over a large range of C⁰_p/C⁰_d values using spectroscopic methods (UV absorption and visible fluorescence emission spectra), equilibrium and sedimentation dialysis, potentiometric and viscosimetric titrations. All the results show qualitative agreement with those obtained previously with the system crystal violet-PMA although the binding seems to be less strong for auramine O than for crystal violet. From dialysis experiments binding isotherms were obtained at three different degrees of neutralization α'; at α' = 0.10 the results could be fitted to a Langmuir isotherm but at α' equal to 0.40 and 0.65 deviations with respect to such an isotherm occur. The results of potentiometric and viscosimetric titrations confirm that the conformational transition which the dye-free PMA exhibits upon ionization is affected by the dye binding. The region in which the conformational transion occurs is broadened and is less sharply defined in the presence of auramine O.