Mechanism of glycan receptor recognition and specificity switch for avian, swine, and human adapted influenza virus hemagglutinins: a molecular dynamics perspective.

Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to prefer avian and human glycan receptor analogues with distinct topological profiles, pentasaccharides LSTa (alpha-2,3 linkage) and LSTc (alpha-2,6 linkage), in comparative molecular dynamics studies. On the basis of detailed analyses of the dynamic motions of the receptor binding domains (RBDs) and interaction energy profiles with individual glycan residues, we have identified approximately 30 residue positions in the RBD that present distinct profiles with the receptor analogues. Glycan binding constrained the conformational space sampling by the HA. Electrostatic steering appeared to play a key role in glycan binding specificity. The complex dynamic behaviors of the major SSE and trimeric interfaces with or without bound glycans suggested that networks of interactions might account for species specificity in these low affinity and high avidity (multivalent) interactions between different HA and glycans. Contact frequency, energetic decomposition, and H-bond analyses revealed species-specific differences in HA-glycan interaction profiles, not readily discernible from crystal structures alone. Interaction energy profiles indicated that mutation events at the set of residues such as 145, 156, 158, and 222 would favor human or avian receptor analogues, often through interactions with distal asialo-residues. These results correlate well with existing experimental evidence, and suggest new opportunities for simulation-based vaccine and drug development

Conserved Daily Transcriptional Programs in Carica papaya

Most organisms have internal circadian clocks that mediate responses to daily environmental changes in order to synchronize biological functions to the correct times of the day. Previous studies have focused on plants found in temperate and sub-tropical climates, and little is known about the circadian transcriptional networks of plants that typically grow under conditions with relatively constant day lengths and temperatures over the year. In this study we conducted a genomic and computational analysis of the circadian biology of Carica papaya, a tropical tree. We found that predicted papaya circadian clock genes cycle with the same phase as Arabidopsis genes. The patterns of time-of-day overrepresentation of circadian-associated promoter elements were nearly identical across papaya, Arabidopsis, rice, and poplar. Evolution of promoter structure predicts the observed morning- and evening-specific expression profiles of the papaya PRR5 paralogs. The strong conservation of previously identified circadian transcriptional networks in papaya, despite its tropical habitat and distinct life-style, suggest that circadian timing has played a major role in the evolution of plant genomes, consistent with the selective pressure of anticipating daily environmental changes. Further studies could exploit this conservation to elucidate general design principles that will facilitate engineering plant growth pathways for specific environments

Webs of influence: the psychology of online persuasion : the secret strategies that make us click

Globin-coupled diguanylate cyclases contain globin, middle, and diguanylate cyclase domains that sense O2 to synthesize c-di-GMP and regulate bacterial motility, biofilm formation, and virulence. However, relatively few studies have extensively examined the roles of individual residues and domains of globin-coupled diguanylate cyclases, which can shed light on their signaling mechanisms and provide drug targets. Here, we report the critical residues of two globin-coupled diguanylate cyclases, EcGReg from Escherichia coli and BpeGReg from Bordetella pertussis, and show that their diguanylate cyclase activity requires an intact globin domain. In the distal heme pocket of the globin domain, residues Phe42, Tyr43, Ala68 (EcGReg)/Ser68 (BpeGReg), and Met69 are required to maintain full diguanylate cyclase activity. The highly conserved amino acids His223/His225 and Lys224/Lys226 in the middle domain of EcGReg/BpeGReg are essential to diguanylate cyclase activity. We also identified sixteen important residues (Leu300, Arg306, Asp333, Phe337, Lys338, Asn341, Asp342, Asp350, Leu353, Asp368, Arg372, Gly374, Gly375, Asp376, Glu377, and Phe378) in the active site and inhibitory site of the diguanylate cyclase domain of EcGReg. Moreover, BpeGReg266 (residues 1-266) and BpeGReg296 (residues 1-296), which only contain the globin and middle domains, can inhibit bacterial motility. Our findings suggest that the distal residues of the globin domain affect diguanylate cyclase activity and that BpeGReg may interact with other c-di-GMP-metabolizing proteins to form mixed signaling teams

Analysis and construction of pathogenicity island regulatory pathways in Salmonella enterica serovar Typhi

Signal transduction through protein-protein interactions and protein modifications are the main mechanisms controlling many biological processes. Here we described the implementation of MedScan information extraction technology and Pathway Studio software (Ariadne Genomics Inc.) to create a Salmonella specific molecular interaction database. Using the database, we have constructed several signal transduction pathways in Salmonella enterica serovar Typhi which causes Typhoid Fever, a major health threat especially in developing countries. S. Typhi has several pathogenicity islands that control rapid switching between different phenotypes including adhesion and colonization, invasion, intracellular survival, proliferation, and biofilm formation in response to environmental changes. Understanding of the detailed mechanism for S. Typhi survival in host cells is necessary for development of efficient detection and treatment of this pathogen. The constructed pathways were validated using publically available gene expression microarray data for Salmonella