The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Dual Infection and Superinfection Inhibition of Epithelial Skin Cells by Two Alphaherpesviruses Co-Occur in the Natural Host

Hosts can be infected with multiple herpesviruses, known as superinfection; however, superinfection of cells is rare due to the phenomenon known as superinfection inhibition. It is believed that dual infection of cells occurs in nature, based on studies examining genetic exchange between homologous alphaherpesviruses in the host, but to date, this has not been directly shown in a natural model. In this report, gallid herpesvirus 2 (GaHV-2), better known as Marek’s disease virus (MDV), was used in its natural host, the chicken, to determine whether two homologous alphaherpesviruses can infect the same cells in vivo. MDV shares close similarities with the human alphaherpesvirus, varicella zoster virus (VZV), with respect to replication in the skin and exit from the host. Recombinant MDVs were generated that express either the enhanced GFP (eGFP) or monomeric RFP (mRFP) fused to the UL47 (VP13/14) herpesvirus tegument protein. These viruses exhibited no alteration in pathogenic potential and expressed abundant UL47-eGFP or -mRFP in feather follicle epithelial cells in vivo. Using laser scanning confocal microscopy, it was evident that these two similar, but distinguishable, viruses were able to replicate within the same cells of their natural host. Evidence of superinfection inhibition was also observed. These results have important implications for two reasons. First, these results show that during natural infection, both dual infection of cells and superinfection inhibition can co-occur at the cellular level. Secondly, vaccination against MDV with homologous alphaherpesvirus like attenuated GaHV-2, or non-oncogenic GaHV-3 or meleagrid herpesvirus (MeHV-1) has driven the virus to greater virulence and these results implicate the potential for genetic exchange between homologous avian alphaherpesviruses that could drive increased virulence. Because the live attenuated varicella vaccine is currently being administered to children, who in turn could be superinfected by wild-type VZV, this could potentiate recombination events of VZV as well

A novel online food recall checklist for use in an undergraduate student population : a comparison with diet diaries

Peer reviewedPublisher PD

A new world typology of cities and systems of cities

The chapter proposes an overview of global urbanization since 1950, relying on the structural and dynamic principles of the evolutionary theory of urban systems and on the observations of some of the major financial linkages connecting cities. We analyze first an overview of the state of urbanization at the world scale using statistics collected and provided for all 195 nation-states of the United Nations. We then examine the extent to which the income level and human development index of countries are correlated with the urbanization rates. Trajectories of cities underline the booming cities including many Asiatic and African cities opposed to the relative declining cities. The total weight of emerging metropolises mostly located in Southern countries passed the total population of the other groups of relatively declining cities between 1980 and 2010. It is highly critical for the urban future that the large majority of urban citizens of the world (more than 60%) will be living in these emerging cities in 2030. It will require finding adapted ways to manage urban growth and ecological transition in these developing systems. This global approach finally leads to the partition of the world we used in the book to analyze more precisely the evolution of individual national or continental urban systems

Qxpak.5: Old mixed model solutions for new genomics problems

Mixed models have a long and fruitful history in statistics. They are pertinent to genomics problems because they are highly versatile, accommodating a wide variety of situations within the same theoretical and algorithmic framework. Qxpak is a package for versatile statistical genomics, specifically designed for sophisticated quantitative trait loci and association analyses. Multiple loci, multiple trait, infinitesimal genetic effects, imprinting, epistasis or sex linked loci can be fitted. The new version (v. 5) allows us, among other new features, to include either relationship matrices obtained with molecular information or user defined matrices that can be read from an input file. This feature can be used for genome selection or - more importantly - to correct for population structure in association studies. In crosses, two parental lines, not necessarily inbred, can be accommodated. This software aims at simplifying statistical genetic analyses implementing a coherent and unified approach by mixed models. It provides a tool that can be used in a wide variety of situations with ample genetic and statistical modeling flexibility. The software, a complete manual and examples are available at http://www.icrea.cat/Web/OtherSectionViewer.aspx?key=485&titol=Software:Qxpak.

Genetic analysis of variation in human meiotic recombination

The number of recombination events per meiosis varies extensively among individuals. This recombination phenotype differs between female and male, and also among individuals of each gender. In this study, we used high-density SNP genotypes of over 2,300 individuals and their offspring in two datasets to characterize recombination landscape and to map the genetic variants that contribute to variation in recombination phenotypes. We found six genetic loci that are associated with recombination phenotypes. Two of these (RNF212 and an inversion on chromosome 17q21.31) were previously reported in the Icelandic population, and this is the first replication in any other population. Of the four newly identified loci (KIAA1462, PDZK1, UGCG, NUB1), results from expression studies provide support for their roles in meiosis. Each of the variants that we identified explains only a small fraction of the individual variation in recombination. Notably, we found different sequence variants associated with female and male recombination phenotypes, suggesting that they are regulated by different genes. Characterization of genetic variants that influence natural variation in meiotic recombination will lead to a better understanding of normal meiotic events as well as of non-disjunction, the primary cause of pregnancy loss. © 2009 Chowdhury et al

Reconnection dynamics and mutual friction in quantum turbulence

We investigate the behaviour of the mutual friction force in finite temperature quantum turbulence in 4He, paying particular attention to the role of quantized vortex reconnections. Through the use of the vortex filament model, we produce three experimentally relevant types of vortex tangles in steady-state conditions, and examine through statistical analysis, how local properties of the tangle influence the mutual friction force. Finally, by monitoring reconnection events, we present evidence to indicate that vortex reconnections are the dominant mechanism for producing areas of high curvature and velocity leading to regions of high mutual friction, particularly for homogeneous and isotropic vortex tangles