Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Apr 2007
Comparative StudySimultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution.
The HA1 domain of HA, the major antigenic protein of influenza A viruses, contains all of the antigenic sites of HA and is under continual immune-driven selection. To resolve controversies on whether only a few or many residue sites of HA1 have undergone positive selection, whether positive selection at HA1 is continual or punctuated, and whether antigenic change is punctuated, we introduce an approach to analyze 2,248 HA1 sequences collected from 1968 to 2005. ⋯ Strikingly, 88 of the 95 substitutions occurred in groups, and multiple mutations at antigenic sites sped up the fixation process. Our results suggest that positive selection has been ongoing most of the time, not sporadic, and that multiple mutations at antigenic sites cumulatively enhance antigenic drift, indicating that antigenic change is less punctuated than recently proposed.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2007
The importance of the Montreal Protocol in protecting climate.
The 1987 Montreal Protocol on Substances that Deplete the Ozone Layer is a landmark agreement that has successfully reduced the global production, consumption, and emissions of ozone-depleting substances (ODSs). ODSs are also greenhouse gases that contribute to the radiative forcing of climate change. ⋯ The climate protection already achieved by the Montreal Protocol alone is far larger than the reduction target of the first commitment period of the Kyoto Protocol. Additional climate benefits that are significant compared with the Kyoto Protocol reduction target could be achieved by actions under the Montreal Protocol, by managing the emissions of substitute fluorocarbon gases and/or implementing alternative gases with lower global warming potentials.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2007
Predicting protein-protein interactions based only on sequences information.
Protein-protein interactions (PPIs) are central to most biological processes. Although efforts have been devoted to the development of methodology for predicting PPIs and protein interaction networks, the application of most existing methods is limited because they need information about protein homology or the interaction marks of the protein partners. In the present work, we propose a method for PPI prediction using only the information of protein sequences. ⋯ The prediction ability of our approach is better than that of other sequence-based PPI prediction methods because it is able to predict PPI networks. Different types of PPI networks have been effectively mapped with our method, suggesting that, even with only sequence information, this method could be applied to the exploration of networks for any newly discovered protein with unknown biological relativity. In addition, such supplementary experimental information can enhance the prediction ability of the method.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2007
Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.
Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. ⋯ AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2007
Innate response to self-antigen significantly exacerbates burn wound depth.
A major component of burn injury is caused by additional local damage from acute inflammation. Using a scald burn model in mice, we find that this part of the injury is dependent on recognition of self-antigen by specific natural IgM, leading to activation of the complement system. We propose that the depth of a burn wound is a sum of the thermal energy applied and of the degree of host inflammatory response.