Genotypic and phenotypic diversity of the noncapsulated Haemophilus influenzae:Adaptation and pathogenesis in the human airways

The human respiratory tract contains a highly adapted microbiota including commensal and opportunistic pathogens. Noncapsulated or nontypable Haemophilus influenzae (NTHi) is a human-restricted member of the normal airway microbiota in healthy carriers and an opportunistic pathogen in immunocompromised individuals. The duality of NTHi as a colonizer and as a symptomatic infectious agent is closely related to its adaptation to the host, which in turn greatly relies on the genetic plasticity of the bacterium and is facilitated by its condition as a natural competent. The variable genotype of NTHi accounts for its heterogeneous gene expression and variable phenotype, leading to differential host-pathogen interplay among isolates. Here we review our current knowledge of NTHi diversity in terms of genotype, gene expression, antigenic variation, and the phenotypes associated with colonization and pathogenesis. The potential benefits of NTHi diversity studies discussed herein include the unraveling of pathogenicity clues, the generation of tools to predict virulence from genomic data, and the exploitation of a unique natural system for the continuous monitoring of long-term bacterial evolution in human airways exposed to noxious agents. Finally, we highlight the challenge of monitoring both the pathogen and the host in longitudinal studies, and of applying comparative genomics to clarify the meaning of the vast NTHi genetic diversity and its translation to virulence phenotypes.

Characterization of nontypable Haemophilus influenzae isolates recovered from adult patients with underlying chronic lung disease reveals genotypic and phenotypic traits associated with persistent infection

Nontypable Haemophilus influenzae (NTHi) has emerged as an important opportunistic pathogen causing infection in adults suffering obstructive lung diseases. Existing evidence associates chronic infection by NTHi to the progression of the chronic respiratory disease, but specific features of NTHi associated with persistence have not been comprehensively addressed. To provide clues about adaptive strategies adopted by NTHi during persistent infection, we compared sequential persistent isolates with newly acquired isolates in sputa from six patients with chronic obstructive lung disease. Pulse field gel electrophoresis (PFGE) identified three patients with consecutive persistent strains and three with new strains. Phenotypic characterisation included infection of respiratory epithelial cells, bacterial self-aggregation, biofilm formation and resistance to antimicrobial peptides (AMP). Persistent isolates differed from new strains in showing low epithelial adhesion and inability to form biofilms when grown under continuous-flow culture conditions in microfermenters. Self-aggregation clustered the strains by patient, not by persistence. Increasing resistance to AMPs was observed for each series of persistent isolates; this was not associated with lipooligosaccharide decoration with phosphorylcholine or with lipid A acylation. Variation was further analyzed for the series of three persistent isolates recovered from patient 1. These isolates displayed comparable growth rate, natural transformation frequency and murine pulmonary infection. Genome sequencing of these three isolates revealed sequential acquisition of single-nucleotide variants in the AMP permease sapC, the heme acquisition systems hgpB, hgpC, hup and hxuC, the 3-deoxy-D-manno-octulosonic acid kinase kdkA, the long-chain fatty acid transporter ompP1, and the phosphoribosylamine glycine ligase purD. Collectively, we frame a range of pathogenic traits and a repertoire of genetic variants in the context of persistent infection by NTHi.

Contribution of genetic and environmental effects on lens thickness: the Guangzhou Twin Eye study.

PURPOSE:

This study investigated the heritability of lens thickness (LT) and relative lens thickness (LT/axial length, rLT) measured by Lenstar among Chinese children and adolescents in the Guangzhou Twin Eye study.

METHODS:

Twins aged 8 to 22 years were enrolled from the Guangzhou Twin Registry. A series of LT and axial length (AL) measurements using the Lenstar were taken for each twin. Zygosity was confirmed by genotyping in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling, after adjustment for age and sex with the Mx program.

RESULTS:

Seven hundred sixty-eight twin pairs (482 monozygotic [MZ] and 286 dizygotic [DZ] twins) were available for data analysis. The mean (standard deviation) LT and rLT were 3.45 (0.18) mm and 0.142 (0.01), respectively. The intraclass correlation coefficients (ICCs) for LT were 0.90 for the MZ and 0.39 for the DZ twins; and those for rLT were 0.90 for the MZ and 0.40 for the DZ twins, respectively. The best-fitting model yielded 89.5% (95% CI: 87.8%-91.0%) of additive genetic effects and 10.5% (95% CI: 9.0%-12.2%) of unique environmental effects for LT, and 89.3% (95% CI: 89.2%-89.3%) of additive genetic effects and 10.7% (95% CI: 10.7%-11.4%) of unique environmental effects for rLT.

CONCLUSIONS:

This study confirms that the LT in young healthy subjects may be mainly affected by additive genetic factors. High heritability remains even when the data are corrected for the influence of AL with the use of rLT.

Statistical Monitoring of Dynamic Multivariate Processes: Part I: Modeling Auto- and Cross-Correlation

The work in this paper is of particular significance since it considers the problem of modelling cross- and auto-correlation in statistical process monitoring. The presence of both types of correlation can lead to fault insensitivity or false alarms, although in published literature to date, only autocorrelation has been broadly considered. The proposed method, which uses a Kalman innovation model, effectively removes both correlations. The paper (and Part 2 [2]) has emerged from work supported by EPSRC grant GR/S84354/01 and is of direct relevance to problems in several application areas including chemical, electrical, and mechanical process monitoring.

Comparison of genetic and morphological methods to detect the presence of American lobsters, Homarus americanus H. Milne Edwards, 1837 (Astacidea: Nephropidae) in Norwegian waters

American lobsters (Homarus americanus H. Milne Edwards, 1837) are imported live to Europe and should according regulations be kept in land-based tanks until sold. In spite of the strict regulations aimed specifically at preventing the introduction of this species into the NE Atlantic, several specimens of H. americanus have been captured in the wild, especially in Oslofjord, Norway since 1999. One of the great concerns is interbreeding between the introduced American species and the local European lobster, H. gammarus (Linnaeus, 1758). For this reason an awareness campaign was launched in 2000 focusing on morphologically "unusual" lobsters caught in local waters. Morphological characters have been based on colour and sub-ventral spines on the rostrum. Two samples of H. americanus were used for comparisons, as well as samples of European lobster from Oslofjord collected in 1992. Previous genetic analyses (allozymes, mtDNA and microsatellite DNA) have demonstrated that the American lobster is distinct from its European counterpart, with several additional alleles at many loci in addition to different allelic frequency distribution of alleles of "shared" alleles. During the present study, thirteen microsatellite loci were tested in the initial screening, and the three most discriminating loci (Hgam98, Hgam197b and Hgam47b) were used in a detailed comparison between the two species. A total of 45 unusual lobsters were reported captured from Ålesund (west) to Oslofjord (southeast) from 2001 to 2005 and these were analysed for the three microsatellite loci. Nine specimens were identified as American lobsters. Comparisons between morphological and genetic characteristics revealed that morphological differences are not reliable in discrimination the two species, or to identify hybrids. Further, some loci display almost no overlapping in allele frequency distribution for the reference samples analysed, thus providing a reliable tool to identify hybrids.

Polarization and Angular Correlation Studies of X-Rays Emitted in Relativistic Ion-Atom Collisions

Particle and photon polarization phenomena occurring in collisions of relativistic ions with matter have recently attracted particular interest. Investiga- tions of the emitted characteristic x-ray and radiative electron capture radiation has been found to be a versatile tool for probing our present understanding of the dynamics of particles in extreme electromagnetic ¯elds. Owing to the progress in x-ray detector technology, in addition, accurate measurements of the linear po- larization for hard x-ray photons as well as the determination of the polarization plane became possible. This new diagnostic tool enables one today to derive in- formation about the polarization of the ion beams from the photon polarization features of the radiative electron capture process.